LECTURE NOTES ON

ENDOCRINE DISORDERS
 INTRODUCTION

Endocrine disorders are disorders that may be due to the

hyperactivity or hypoactivity of the concerned gland.

 STUDY OF ENDOCRINE DISORDERS

 
An endocrine disorder is studied by analyzing:
1. Causes
2. Signs and symptoms
3. Syndrome.

1. Causes: Endocrine disorder may be due to the hyperactivity or hypo-activity of

the concerned gland. Secretion of hormones increases during hyperactivity and
decreases during hypo-activity.
2. Signs and Symptoms:
A sign is the feature of a disease as detected by the doctor during the physical examination.
So, it is the objective physical evidence of disease found by the examiner.
Examples of signs are;
 yellow coloration of skin and mucous membrane in jaundice,
 paleness in anemia, enlargement of liver, etc.

A symptom is the feature of a disease felt by the patient. So, it is the subjective evidence
perceived by the patient. In simple words, it is a noticeable change in the body, experienced by
the patient. Examples of symptoms are;
fever, itching, swelling, tremor, etc.

3. Syndrome: is the combination of signs and symptoms (associated with a disease), which
occur together and suggest the presence of a certain disease or the possibility of developing the
disease. Examples are Stoke-Adams syndrome and syndrome of inappropriate antidiuretic
hormone hyper-secretion
 PITUITARY GLAND (HYPOPHYSIS)
DISCRIBTION
o Is a small reddish-grey body with an average weight of about 0.5gms in humans.
o It is composed of the anterior lobe or adenohypophysis and the posterior lobe or
neurohypophysis
o The anterior lobe constitutes about 75% of the entire mass of the pituitary gland.

SOME DISORDERS OF THE ANTERIOR PITUITARY;

Excess Growth hormone secretion;
Excessive secretion of the Growth hormone as is seen in adenomas of the pituitary is
associated with acromegaly or gigantism depending on when the excess secretions occur
a) ACROMEGALY;
o is a clinical condition which arises when excessive growth hormone
secretions occur after the closure of the epiphysis of the long bones.
Signs and symptoms include-
o Overgrowth of the palms, jaws,
o thick lips thick hands thick toes and other chimpanzee-like features
o Because of the accompanying excess secretion of associated hormones e.g.
ACTH, such individuals also have highly pigmented skin.
 Visual field changes /(bitemporal hemianopia)

Typical Findings in acromegaly

b) Gigantism

Occurs when excess secretion occurs before the closure of the

epiphyses, the individual is left with a clinical condition known as
gigantism. In addition to some or all of the mentioned features of
acromegaly, the individual has:
•Enlarged sella tursica, the location of the hypophysis.
•Headaches.
•Visual defects e.g. ocular pulses, optic atrophy, papilledema
•Diabetes insipidus, presenting as polyuria.
•Affected individuals usually get better when the tumour is
surgically removed.
ADRENAL/SUPRARENAL GLANDS

Are two small glands embedded in fat above the kidneys. Each gland is divided

into a cortex and a medulla

Adrenal medulla;
Is the central portion of the gland and constitutes about 20% of the entire gland. It
consists of chromaffin cells which contain granules

ADRENAL CORTEX;
 
Is the outer portion of the adrenal gland and consists of 3 regions from outside to
inside, a zona glomerulosa, a zona fasciculate and a zona reticularis
DISEASE ASSOCIATION WITH THE ADRENAL CORTEX

Cushing's syndrome (Adrenocortical Hormone Excess )

Cushing's syndrome is the term used to describe the clinical entity associated with
prolonged excessive circulating levels of any glucocorticoid. A few of these patients also
have clinical features associated with prolonged excessive circulating androgens

The possible causes include but not limited to the following

i. Adenoma of the adrenal cortex

ii. Pituitary dependent bilateral adrenocortical hyperplasia
iii. Carcinomas of the adrenal cortex
iv. May arise from treatment with excess doses of natural orsynthetic corticosteroids.
 
Adrenogenital syndrome in a 4 year old boy
 Signs / Symptoms of Disorder

The signs and symptoms most associated with this condition (Cushing's syndrome) are the
following:

i. Hypertension
ii. Oligomenorrhoea in woman
iii. Polyuria and diabetes like symptoms
iv. Obesity mainly in the face and the trunk
v. Muscle weakness and Hirsutism
vi. Excessive bruising
vii. Osteoporosis and spontaneous fractures

As earlier observed, the obesity is prominent in the chest and head regions where excessive
deposition of fat takes place. There is, therefore, a characteristic appearance of fat deposition at
the neck, trunk, thoracic and upper abdominal regions, the so-called "buffalo hump" or "buffalo
torso" and a round smooth face, the so called "moon-face".
Diagnosis of Cushing's syndrome

oDiagnosis is quite obvious from the clinical history and prevailing signs and
symptoms.

oAdded to that is the fact that the Cortisol response to insulin-induced hypoglycemia
is absent in such individuals.

oIn addition, normal circadian rhythm rules out Cushing's syndrome in suspected
patients.
Adrenocortical insufficiency

This disorder is of two classifications

i. Primary adrenal insufficiency

is the term when the disorder is due to the destruction or damage to the adrenal glands
per se and

ii. Secondary insufficiency

is the term when the disorder is due to hypothalamic or pituitary disease, which result in
impaired ACTH secretion and subsequent adrenocortical
atrophy.
oAcute hypoadrenalism of short duration may be uncommon but usually a
life-threatening problem that needs urgent attention.

oBecause of its importance, chronic hypoadrenalism made headlines in 1855

when Thomas Addison first described it.

oHence the name, Addison's disease, was given to all forms of chronic
hypoadrenalism.
 
 Addison's disease

Is a term given to describe all forms of chronic hypoadrenalism.

Causes of Addison's disease

oIn the days of Addison, tuberculosis was the most common cause of chronic
hypoadrenalism.

oIn the 20th century, studies of autoimmune phenomena in endocrine glands

resulted in the discovery that autoimmune adrenalitis was responsible for most cases
of hvpoadrenalism.

oUncovered were an array of facts, which included the identification of circulating

auto-antibodies to the adrenal cortex.
Signs / Symptoms of Addison's Disease

These include:
oWeakness, tiredness, lethargy, postural hypotension

oAnorexia, weight loss and nausea

oHyperpigmentation, due to raised levels of ACTH whichimmensely helps in diagnosis

oAbdominal pain and dyspepsia

oMental disturbance
Diagnosis:

oLow levels of circulating Cortisol constitute a clue to diagnosis.

oIn severe cases, random Cortisol level in the early morning hours (07 to 09
hours) are rather reduced.

oManagement

Management of patients with primary hypo-adrenalism depends to a great

extent on permanent replacement therapy with both mineralocorticoids and
glucocorticoids.
Aldosteronism

oAldosteronism refers to the clinical entity associated with excessively

circulating levels of aldosterone.

oThe disorder is of two classifications;

a. Primary aldosteronism;
is the classification when excessive circulating levels of aldosterone are due to
intrinsic disease of the adrenal gland

b. Secondary aldosteronism
is the term when excessivelevels in circulation are due to excessive
stimulation of the gland by extra adrenal factors; e.g. by a tumour of the
hypothalamus or the anterior pituitary gland.
Primary aldosteronism (Conn's disease)

In 1954, Conn first described the entity known as primary aldosteronism;

hence the disorder is today known as Conn's disease. The disease is
uncommon. Adrenal adenoma was responsible for most of the cases.

Causes of primary aldosteronism

include but are not limited to:

oAdrenal hyperplasia

oAdrenal adenoma

oAdrenal carcinoma
 Signs/symptoms of primary aldosteronism

i.Hypertension, which perhaps is due to increased extracellular volume caused

by increased sodium and subsequent water reabsorption.

ii.Hypokalemia with associated effects such as overt or latent tetany, flaccid

paralysis, paresthesia, and muscle weakness.

iii.Polydipsia, polyuria and nocturia.

When not diagnosed and treated early, the patient may become worse and
complications such as myocardial infarction and stroke may set in and sometimes
death may follow.
Diagnosis

Consistent low levels of plasma potassium (K+), which correlate

positively with previously mentioned signs and symptoms are
diagnostic.

Management
Confirmed cases of primary aldosteronism may be managed with
spironolactone, an important antagonist to aldosterone.
 
DISEASE ASSOCIATION WITH THE ADRENAL MEDULLA;

Excess catecholamine secretion is associated with

•Phyeochromcytoma
• Neuroblastoma
•Sympathoblastoma
•Chymodectoma
• Ganglioneuroma
•Retinoblastoma
Pheochromocvtoma

Is the most important adrenomedullary tumour.

It may arise from the remnants of pheochroblasts, the precursors of the

chromaffin cells

Pheochromocytoma occurs equally in both sexes and

Usually manifests during the third and fourth decades of life.

Manifestations of pheohromocytoma are due either

o to the release of excess catecholamines by the chromaffin cells or

o to the ill-effects of tumorous tissues on surrounding cells.

Signs and Symptoms

Signs and Symptoms of excess circulating catecholamines are essentially the

same as those produced by the injection of excessive norepinephrine and
include:
i. Hypertension
ii. Headaches, anxiety and palpitations
iii. hyper metabolism, weight loss, weakness and fatigue
iv. hyperglycaemia, diabetes-like symptoms e.g.
glucosuria
v. pyrexia
Diagnosis of Pheochromocytoma

Diagnosis is often made in young hypertensives (aged below 40) whose clinical
history, signs and symptoms correlate with high levels of serum catecholamines or
their metabolites.

Such symptoms could be

ovanlly-mandelic acid (VMA) and or metanephrine.

oHigh levels of urinary dopamine and or its metabolite,

o homovanillic acid excretion usually suggest the diagnosis of pheochromocytoma.

Management

In the treatment of endocrine disorders, (clinical therapeutics) patients may

likely benefit if laced on adrenergic antagonists.

Such antagonists are usually instituted before invasive procedures, surgery, etc.
which can take care of tumorous tissue
 THE THYROID GLAND

oThe thyroid gland is located just below the larynx.

oIt consists of 2 lobes positioned on each side of the trachea and connected to each
other interiorly by a thick line of connective tissue called the isthmus.

o It weighs about 20-25gms.

oThe gland is made-up of small spherical hollow sacs called the thyroid follicles which
contain follicular cells that synthesis the thyroid hormone, thyroxin.

oWithin the follicles, is a protein-rich fluid called the colloid.

oIn addition to follicular cells, the thyroid gland also contain parafollicular cells which
secrete the hormone calcitonin
 Disorders of Thyroid Gland
Hyperthyroidism, hypothyroidism, Graves' disease and goiter are the
most important disorders of the thyroid,

Hyperthyroidism;

Refers to disorders associated with increased secretion of the thyroid

hormone.
Causes;
•Toxic adenoma
•Multinodular goitre
•Graves’ disease
Patient with Exophthalmos; Hyperthyroidism
 Graves' Disease

Graves' disease is a syndrome comprising hyperthyroidism, bulging eye balls f

exophthalmos) diffuse goiter, and in a few cases, localized myxoedema (skin
dryness),

 Not all these components may be present in an individual patient, but

exophthalmos and the enlargement of the thyroid gland appear to be very important
in the identification of Graves disease.

Graves' disease is predominantly a female problem and usually debuts between

the third and fifth decades of life.

The disorder is one of these diseases in which an individuals immune system may
have turned against itself, producing thyroid stimulating antibodies that readily mimic
the effect of thyroid stimulating hormone.

Unfortunately, the gland responds to the stimulating effect of these

autoantibodies, producing and secreting unrequired thyroid hormones.
Signs and Symptoms of Graves' Disease

The following areas are affected

The eyes increase in size and bulge from their sockets, a condition clinically referred to
as exophthalamos.

The thyroid gland is enlarged and clinically referred to as goiter.

Changes in the skin pigmentation and texture (dryness of the skin, clinically called
myxoedema)
 The effect of increased circulating thyroid hormones, which will result in exaggerated
actions of the hormones, include.

i. Heat intolerance, increased sweating, warmmoist skin, fever / hyperpyrexia

ii. Increased catabolism, weight loss, even withtachycardia
iii. Irritability, nervousness and, rarely, evenpsychoses and paranoia
iv. Increased linear growth in children
v. Muscular weakness, easy fatigability, pruritis and loss-ofhair.
Diagnosis of Graves' Disease

The signs and symptoms of Graves' disease are obvious and so diagnosis constitutes
no problem. The protruding eye balls, the clearly enlarged thyroid gland and, in some
cases, the skin signs, complimented by a few thyroid function tests make the
diagnosis quite easy.

In fortunate patients, the hyperthyroidism responds to anti-thyroid drugs.

In others, partial removal of the thyroid gland (partial thyroidectomy) is the last
resort after an initial treatment with anti- thyroid drugs.
Hypothyroidism

The term may refer to low levels of circulating thyroid hormones (T3 and T4)
and rarely to deficiency of actions of circulating thyroid hormones at the tissue
level.

In Europe and the Americas, most cases of hypothyroidism are due to
autoimmune thyroid disease.

 In a few cases during partial thyroidectomy, more than enough thyroid

tissue is removed predisposing the individual to hypothyroidism.

A few cases, especially in developing countries, are due to iodine deficiency

with resultant endemic goiter. H

ypothyroidism is also more common in females

Hypothyroidism: Myxoedema
Signs and symptoms of Hypothyroidism

Weight gain, even with underlying anorexia and constipation

Hoarseness of the voice

Dryness of the skin, facial puffiness, myxoedema

Prolongation of the relaxation phase of the tendon reflex, slow pulse rate

Hypometabolism and lack of energy

Cold intolerance

Anaemia
In overt hypothriodism, many other tissues are affected.

The cardiac output is usually reduced due to decreased stroke volume

and heart rate.

Turnover of both Cortisol and aldosterone is decreased.

The autoimmune phenomenon of the thyroid may be associated with the

same factors as in other endocrine glands. For example, in the endocrine
pancreas that may result in insulin-dependent diabetes mellitus in the
same individual, his autoantibodies antagonize his endogenous insulin or
his pancreas.
Diagnosis

Diagnosis of overt hypothyroidism is simple because of the obvious signs and

symptoms.

In addition, the serum free T3 is invariably low. However, the level of free T3 may be
normal.

The serum level of TSH is usually elevated. Normal serum level of TSH excludes the
diagnosis of hypothyroidism on the basis of primary thyroid disease.

Supplementary thyroid hormone will be beneficial to this patient.

Replacement therapy may be life long, depending on the degree of destruction of

thyroid tissue.

 Treatment modalities may rightly depend on other organs that may be affected e.g.
the adrenal gland
Goiter

The term goiter refers to an enlargement of the thyroid gland.

The size of the thyroid gland may vary from one geographic area to
another .

Therefore, a more precise definition may be appropriate.

Some cases of goiter are idiopathic; others are due to specific factors.

Goiters tagged to specific causes are the following:

i. Endemic goiter; due to dietary iodine deficiency.

ii. Drug induced goiter
iii. Dishormogenicgoiter
iv. Reidel's thyroiditis
v. Superlative thyroiditis
vi. Sub-acute thyroiditis

When there is inadequate thyroid hormone secretion, there is increased over-

production of TSH, a mechanism embarked upon by the body to stimulate the
thyrotrophs to produce more thyroid hormones.

The effect of the excess TSH is the enlargement of the thyroid gland
Endemic Goiter
This refers to goiter caused by iodine deficiency.

Most cases of endemic goiter are seen in mountainous areas especially those far
from the sea where iodine content of food is low.

 Even in these mountainous areas, not everyone is goitrous which essentially

means that there may be other additive factors.

Fluorides, contaminated water and genetic factors have been mentioned as possible
additional factors.
Some cases are due to defects in the iodine pump. But this is rare.

Others may be due to organification defects.

Therefore, enough iodine could be present in the diet in this case, but its
organification is defective.

Other abnormalities in the stages of synthesis of thyroid hormones, which can

increase the incidence of endemic goiter, are:
a. Iodine transport defect
b. Coupling defect
c Dehalogenase enzyme defect
d. Defect in thyroglobulin formation
e. Abnormalities of thyroid hormone binding protein
Drug Induced Goiter:

Some substances (chemicals, drugs, foods,) may cause goiter in genetically predisposed
individuals.

Such substances are known as goitrogens.

The following substances are known to cause goiter in individuals especially when
taken in large amounts for long periods:
Foods:
i. Cassava
ii. Soya Beans
iii. Edible nuts
iv. Brassicacae plants (e.g. Cabbage)

Drugs, which may cause goiter, include:-

i. Cobalt
ii. Ethionamide
iii. Resorcidol
iv. Iodine
v. Lithium
vi. Thiocynate
vii. Sulphonamides.
Goitrogens cause goiter by;

 interfering with the synthesis of thyroid hormones (thyroxine, and tri-iodothyronine).

 The interference of these substances on the synthesis process of thyroid hormones

results in continuous stimulation of the thyroid tissue by the thyroid-stimulating
hormone (TSH) from the anterior pituitary.

 The continuous stimulation causes the hypertrophy of the thyroid gland otherwise
known as goiter.

 Goitrogens produce anti-thyroid action and the goitrous thyroid regresses on

withdrawal of the goitrogen.
The following drugs are used in the treatment of thyrotoxicosis.

Drugs:
i. Methimazole
ii. Propylthiouracil
iii. Carbimazole
iv. Per Chlorate
 THE PARATHYROID GLANDS

There are four parathyroid glands two each located on the dorsal surface of the
thyroid glands one above each of the upper and one below each of the lower poles of
the thyroid.

DISEASES OF THE PARATHYROID GLAND

1. Hyperparathyroidism:

Hyperparathyroidism is defined as a state of excessive circulating parathyroid

hormone.

The disorder is uncommon both in the developed and developing worlds.

A proper definition of the cause of this disorder has not been made.
However, some experts think that radiation to the head and or/ neck region early in
life may predispose an individual to parathyroid hyperplasia and adenoma which may
present many years later.

The radiation may predispose the individual not only to parathyroid adenoma and
hyperplasia but also to adenomata of other tissues in the vicinity of the parathyroids
e.g. the pituitary and thyroid glands but even the pancreas and the adrenal gland.
Diagnostic Features:

As may be expected, this disease shows prominently at one of the sites of action of
PTH, the bones.

There could be overt bone disease, but also, the disorder may be asymptomatic.

In hyperparathyroidism, bone loss is accelerated which may or may not show in bone
radiographs.

Radiological investigations of bones in this case may show evidence of decreased bone
density.

On the kidneys, evidence of hyperparathyroidism may be found in the form of

nephrocalcinosis, calculi and glomerular / tubular dysfunction.

The cause of these abnormalities in the kidneys may be the high circulating calcium
ions. Other signs and symptoms of hyperparathyroidism include:
i. Anorexia, vomiting and fatigue
ii. Weight loss, constipation
iii. Polydipsia and polyuria
iv. Proximal myopathy
v. Hypertension, pancreatitis
vi. Zolllinger Ellison syndrome
vii. Pruiritus
viii.Mental changes
ix. Renal failure
Diagnosis of Hyperparathyroidism

There are reports of normocalcemic hyperparathyroidism, but this is not the norm.

In the majority of cases, there are elevated levels of calcium ions in the extracellular
fluid of hyperparathvroid patients.

Diagnosis of hyperparathyroidism is incomplete without efficient measurement of

serum calcium levels.

Elevated levels of immuno-active plasma PTH are also a strong indication of

hyperparathyroidism.

However, it is not unusual for low levels of plasma PTH and even inorganic phosphate
to be found in cases of mild hyperparathyroidism.
Treatment

Hyperparathyroidism due to tumours may be managed with the

excision of the gland among other measures, which may be decided
by the attending physician after a careful consideration of individual
factors.
Hypoparathyroidism

Hypoparathyroidism is defined as a failure of the secretion of

parathyroid hormone or failure of its action at the level of the tissues
despite elevated levels of parathormone.

Compared with hyperparathyroidism this disorder is rare.

Current belief is that the disorder is inherited in an autosomal recessive

fashion.

Such individuals may also have inheritable problems of other glands

e.g. the adrenal and thyroid glands.

Remote genetic causes predispose the individual to varying degrees of

autoimmune mechanisms that produce organ-specific autoantibodies with
a preponderance for those against the parathyroid, the thyroids and the
adrenal glands.
SIGNS AND SYMPTOMS

The central features in hypoparathyroidism is hypocalcaemia. It is possible that most of

the signs and symptoms of the disease arise from the effects of hyocalcaemia on various
tissues. The signs and symptoms associated with severe cases are:

i. Tetany
ii. Muscle cramps and stiffness
iii. Tingling in the extremities
iv. Carpopedal spasm
v. Laryngeal stridor and convulsions especially in children
Diagnosis of Hypoparathyroidism

Biochemical studies of plasma from hypoparathyroids will show low levels of both
parathyroid hormone and calcium ions.

 there may be high plasma phosphate and

low levels of alkaline phosphates.

However, differential diagnosis with other possible causes of hyocalcaemia and

hyperphosphatemia e.g.hypomagnesaemia and chronic renal failure, is indicated.

Life threatening tetanic hyocalcaemic episodes may be managed with intravenous

calcium gluconate infusions.
Calcitonin or Thyrocalcitonin

The parathyroids are not the main source of calcitonin.

Large Quantities of the hormone are produced at the parafollicular cells of the thyroid
while minor quantities are produced at the parathyroidr the thymus, the pituitary, the
lungs and the small intestines.

At present, the precise source of the peptide with full biological activity is not clearly
known.

The steps involved in the biosynthesis and the possible precursors are also still unclear.
Syndrome of Calcitonin Excess / Deficiency

Certain tumors produce elevated plasma levels of calcitonin.

These tumours include the following: Zollinger Ellison syndrome, oat cell carcinomas of
the lungs, medullary carcinomas of the thyroid and carcinoid tumours.

There are also elevated plasma levels of calcitonin in pernicious anaemia and renal failure.

Elevated plasma levels of calcitonin will normally result in hypocalcaemia and assorted
signs and symptoms of low plasma calcium levels.

Even in thyroidectomy when the major source of calcitonin is removed, clinically defined
deficiency of calcitonin is not known.

No major disturbance in calcium homeostasis is, as of now, therefore, associated with
calcitonin deficiency.
ENDOCRINE PANCREAS (ISLETS OF LANGERHANS)

The pancreatic islets first described by Langerhans in 1869 are the endocrine component of
the pancreas. These constitute less than 1 to 2% of the pancreatic mass.

Distinguished as major cell types are the beta, - or B cells that secrete insulin,

 the alpha or α cells that secrete glucagon and the delta or D cells that secrete
somatostatin.

The minor cell types recently identified are the PP cells and granular cell types. The PP
cells are known to secrete a hormone of undefined biologic function called the pancreatic
polypeptide
Diabetes Mellitus

Diabetes mellitus may be defined as a heterogenous group of disorders caused by a

deficiency of insulin level in the extracellular fluid or of its actions at the peripheral
tissues.

The classification, on biochemical and clinical grounds which persists till today considers
diabetes in two variants which are:

Insulin-Dependent Diabetes Mellitus (IDDM), type one.

Non-insulin Dependent Diabetes Mellitus, (NIDDM) type two.

In addition to these typical variants, There has since been known a malnutrition-
Related Diabetes Mellitus (MRDM). MRDM is usually insulin dependent and therefore,
may be considered somewhat as a subgroup of insulin dependent diabetes.
Insulin Dependent Diabetes Mellitus

In insulin-dependent diabetes mellitus, there is total deficiency of insulin secretion

and usually this results from, near total absence of beta cells in the islets of
Langerhans.

Evidence available at present indicates that IDDM runs in families and so there may
be a hereditary aspect to the disorder.

Autoimmunity may play an important role in the disease.

In such individuals, there may be the presence of autoantibodies against other organs
like the thyroid and the adrenal glands.

Both the autoantibodies and other ill-defined genetic factors lead to the destruction of
beta cells

The trace amounts of beta cells left are then unable to produce enough insulin
necessary for the metabolism of glucose and other energy giving compounds.
 The individual, as would be expected, then has high levels of circulating
extracellular glucose and other energy-giving substances like fats, and amino acids.

Available evidence indicates that it is the very high circulating glucose

(hyperglycemia') and cholesterol that produce the clinical signs and svmptoms of
insulin-dependent diabetes mellitus.
Diagnostic Features

The main signs and symptoms of IDDM are polydipsia.

polyuria, nocturia, fatigue, anorexa and weight loss.

There may be recurrent infections, which may be initial signs that bring the patient
to the attention of the physician.

Ketoacidosis may be the ugly monster that brings the patient initially to the
emergency room.

Untreated and inadequately treated cases of IDDM produce very serious

complications, which may result in the death of the patient.

The complications, which result in tissue damage in many parts of the body usually,
become evident after many years of the disease.
The main sites of tissue damage are listed here under;

A. The Heart: Ischemic heart disease.

B. The Kidneys: Nephropathy

C. The Blood Vessels:

i. Hypertension
ii. Cerebrovascular disease
iii. Peripheral Vascular disease

D. The Eyes:
i. Retinopathy
ii. Maculopathy
iv. Cataract

E. Musco-Skeletal Tissues:
i. Limited Joint Mobility
ii. Soft tissue thickening
F. Lymphatics: Infections
Diagnosis of IDDM

In 1979, the American National Diabetes Data Group (NDDG) followed by the World Health
Organization (WHO) expert committee on diabetes proposed a standardisation widely
accepted for the diagnosis of the disease. The standardization also includes symptoms of
non-insulin dependent diabetes and glucose intolerance.

Most will show the classical signs and symptoms of polyuria, polydipsia, fatigue and
weight loss.

Ketoacidosis will cause further symptoms in patients who fail to take care of these initial
signs and symptoms of the disease.

The magnitude and severity of these initial classic signs and symptoms may depend on
the magnitude of islet cell destruction, undefined individual determinants and overall
health situation of the patient
A raised blood sugar level is important in diagnosis.

Any individual with a fasting blood sugar level greater than 120 mg/dl (6.6 mmo/) should have an
oral glucose tolerance test to know if the individual is diabetic or not.

Impaired glucose tolerance is the diagnosis if the concentration is equal to or greater than 120
mg/dl: but if the level is 189mg/dl or greater, the diagnosis mav be diabetes mellitus.

Anyhow, this concentration will corroborate the signs and symptoms mentioned above.
Management of insulin-dependent diabetes and indeed other types of diabetes

usually involves an adjustment of the diet of the individual,

exercise at regular intervals, health education,

 measurement of blood glucose level on a regular basis and,

incase of IDDM, supplementary therapy with insulin.

The treatment of IDDM and all other types of diabetes aim to achieve a good metabolic
control with the following characteristics.

•Capillary blood glucose level ranging between 90 and 160mg/dl (5 and 8.8mo/L) in the
fasting state.

•None or trace glucosuria

•Normal weight

• No severe acute complications.

: Differences Between IDDM and NIDDM

Parameter IDDM NIDDM

Age at Onset Bellow 30 years Above 30 Years

Peak age of onset
(a)5 years in developed 60 years in all countries.
countries e.g. Sweden,
Finland, Norway, USA etc.
(b)18 years in the
developing countries e.g
Nigeria.

B cell mass Less than 10% present 50-70% present

Islet cell antibodies Generally present Absent in the majority of cases.

Ketosis cDevelops with insulin withdrawal Occurs with severe stress or in

serious infer tinns

Weight status Weight loss Normal or obese

Rate of onset Rapid Slow
Endogenous insulin secretion Low or absent Reduced
Non-Insulin Dependent Diabetes Mellitus (NIDDM)
Insulin insensitivity and, or resistance characterize this type of diabetes.

In the majority of cases of NIDDM, an acceptable level of insulin secretion is retained
but the amount
may not be sufficient to provide the afflicted with enough energy.

 Not equipped with the needed machinery for insulin sensitive receptors to enhance the
entry of glucose and other energy giving substrates into tissues, the individual battles
with the problem of hyperglycemia and hypercholesterolemia that produce symptoms.

Obesity is associated with NIDDM, though not all cases.

In obese NIDDM patients, research findings indicate that loss of excess weight is
associated with a normalcy of insulin secretion.

However, low insulin secretion not being the whole story, diabetes may still be
present in a variant of this disease where receptor insensitivity or inadequacy of
insulin receptor is the predominant pathology.

 In tribes where there is high prevalence of obesity, NIDDM is very common.

This is the case of the Indian Americans especially those living in the mountainous
regions of Alaska.

There is a genetic predisposition to NIDDM.

Indeed, recently, investigators have revealed that there is greater genetic

relationship in NIDDM than in IDDM. Hence NIDDM runs in families.

NIDDM may not be an autoimmune disease. This is the conclusion reached from
studies of auto-antibodies in the blood of NlDDM patients.
 Diagnostic Features of NIDDM
The signs and symptoms of NIDDM which may not be radically different from
those of IDDM are as follows:-
i. Polydipsia
ii Polyuria
iii Nocturia
iv Fatigue
v Myalgia
 Complications, which are also not different from those of IDDM patients include:

i Hypertension
ii Retinopathy
iii Nephropathy
iv Cataract
v Neuropathy
vi Limited joint motility
vii Leg and mouth ulcers
viii Frequent stroke
ix Cardiac failure
x Frequent infections.

Diagnosis of non-insulin dependent diabetes takes the same pattern as that of insulin
dependent diabetes mellitus.
 Malnutrition Related Diabetes Mellitus (MRDM)

Hugh Jones first described this atypical diabetes mellitus in 13 Jamaican patients
in 1955.

Zuidema described a similar variety in several Indonesian patients in 1959.

 Late in the last century, Oli and Nwokolo described this atypical variety in
Nigerian patients.

The variant was given different names by different investigators.

It was first called Jamaican "J" diabetes by Hugh Jones while several others that
followed nicknamed it tropical diabetes because a majority of the patients lived in the
tropics.

Most recently a WHO report and that of the American DiabAes Data Group gave
the name, malnutrition-related diabetes mellitus (MRDM). Most adult Nigerian patients
fall in this group.
 The causes of MRDM is unknown.

In the variant which Oli and Nwokolo described, "Inspissated" plugs caused by infections
followed bv severe malnutrition is said to plug the pancreatic ducts resulting in pancreatitis.

During this scenario, a good number of islet cells are lost. The degree of loss may decide if
the individual so affected will become diabetic or not

There also may be a genetic predisposition as was found in two separate studies by Afoke
and Famuyiwa (1986).

In Nigerian patients, there was also an abundance of auto-antibodies like islet cell antibodies
and islet cell surface antibodies.

And since even larger doses of insulin are needed in the treatment of these patients, MRDM
may just represent a tropical variant of IDDM that appears to ravage malnourished populations
whose general resistance to diseases is weakened. Cassava is also theorized to be a causative
factor for MRDM. But whether this is a malady that targets only poverty-stricken populations is yet
to be clarified.
 Diagnostic Features

Signs and symptoms of MRDM are many and varied. They include much of the
previously mentioned signs and symptoms. In addition, the individual also has:
i Intraductal calculi
ii Pancreatitis
iii Lean body mass.
iv No ketosis

Diagnosis of this variant of diabetes entails the putting together of the mentioned
signs and symptoms and careful history of the patients. Management of this type of
diabetes is the same as that of IDDM.
Hypoglycemia

This term refers to low levels of circulating glucose in the extracellular fluid.

 Chronic types occur less often than the hypoglycemia which characterizes diabetes
mellitus.

Normal fasting sugar level may be different from one geographical area to another and
this may even depend on the types of foods eaten.

An average, anyway, may be a fasting blood glucose of between 50 and 90mg-dl (2.8
and 5 mmo/L).

Hypoglycemic episodes may be frequent in alcoholics because, perhaps, of poor eating

habits or due to poorly understood individual determinants. Acute Hypoglycemia is just
as bad as, if not worse than, hyperglycemia especially when treatment is not given.
The symptoms, which are characteristic of hypoglycemia, include,

•Sweating, Hunger, Palour, Palpitations

•Headaches, Tachycardia, Tremor and unguarded gait

•High blood pressure (not in all cases) and may be due to epinephrine release,
Restlessness

•Visual symptoms e.g Diplopia

•Numbness, Convulsions
A variety of factors may cause hypoglycemia, notable among them are:

• Poisoning with a number of substances: monoamine oxidase inhibitors, ackee,

antihistamines and salicylates.

• Administration of high doses of insulin or other

hypoglycemic drugs.

• Neoplasms

• Islet cell hyperplasia

•Liver disease

•Glycogen storage disease.

Treatment for hypoglycemia depends on the correct diagnosis of the underlying cause.
THE GONADS

These are some of the most specialized endocrine organs where the male organ is
quite different from that of the female.

The male gonads are called testes and those of females are called ovaries.

Principal hormones secreted by the gonads;

Ovaries; Oestrogen and progesterone

Testes; Testosterone
Disorders Associated with Testosterone Hypersecretion/Deficiency

Defects in testosterone or dihydrotestosterone synthesis can result in hypogonadism in

genetic males.

There could be defects in the formation of enzymes involved in any stage of

testosterone synthesis.

This disorder is rare but could occur.

Usually it occurs as an abnormal recessive trait.

The most common defect involves the enzyme that modulates the conversion of
cholesterol to pregnenolone, an initial pathway in the synthesis of these sex steroids.

Individuals in which this occurs have also defective Cortisol secretion, low plasma
levels of androstenedione, dehydroepiadrosterone and low urinary 17-hydroxysteroids.
Most of such individuals die in infancy from adrenal insufficiency.

On the other hand, defects in androgen action lead to several clinical disorders associated with
deficiencies in virilization and masculinization.

These individuals may have complete androgen insensitivity and testicular feminization.

Usually this is an inherited defect, may be X-linked and run in families.

The individual may still have a 46XY karotype but this is, in fact, only a genetic deception.

These "males" may have a female phenotype and external genitalia with primary amenorrhaea
and scanty or absent pubic hair.

Breasts may well develop as in a normal female.

The testes may be present in the pelvis or groin, may secrete normal male amounts of oestrogen
and testosterone but the actions of the oestrogen are antagonized by those of testosterone which
does not have reactive levels of cytosol testosterone receptors.
Apart from these more common forms of testicular disorders, there is the very rare
condition in which there is rather hypergonadism.

Very few of such cases are mentioned in medical literature.

Such individuals are expected to have exaggerated features with elevated levels of
plasma androgens, excessive libido, erection abnormalites, masculinity, and there
may be alterations in spermatogenesis and other androgen functions.

But in the same individual there may also be excessive circulation of oestradiol,
which opposes the high plasma levels of testosterone.

This means that the female individual may even have normal phenotypic male
features.