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Hypopituitarism (Panhypopituitarism)
Gounden V, Jialal I.

Introduction
The pituitary gland is responsible for the production and secretion of various hormones that play a vital role in regulating endocrine function within the
body. The pituitary gland consists of an anterior and a posterior lobe. Hormones produced by the anterior lobe of the pituitary gland include growth
hormone (GH), thyroid-stimulating hormone (TSH), luteinizing hormone (LH), follicular-stimulating hormone (FSH), adrenocorticotropin (ACTH),
and prolactin (PRL). Hormones stored and released from the posterior pituitary are antidiuretic hormone (ADH)/vasopressin and oxytocin. ADH and
oxytocin are produced by neurosecretory cells in the hypothalamus. Trophic hormones produced by the hypothalamus stimulate or inhibit production
of different anterior pituitary hormones which then effect target organs. See Table 1 (Anterior Pituitary Hormones).

Hypopituitarism is defined as a deficiency of one or more of the hormones produced by the pituitary gland. The presence of hypopituitarism is
associated with increased mortality due to increased cardiovascular and respiratory diseases, and early diagnosis is important to prevent further
morbidity due to the subtle presentation.[1][2][3]

Etiology
The causes of hypopituitarism can be attributed to either pathology of the hypothalamus affecting the production of trophic hormones that act on the
pituitary or direct pathology of the pituitary gland itself. The most common cause of hypopituitarism (61%) is the presence of pituitary tumors (both
non-secretory and secretory). Pituitary tumors may cause the increased production of one hormone with resultant deficiency of the other pituitary
hormones as in acromegaly (excess GH with hypopituitarism from the macroadenoma). Most pituitary tumors are benign and may be secretory or non-
secretory. Secondary metastases originating from, for example, breast, colon and prostate cancers do occur less commonly. Hypothalamic and para-
pituitary tumors such as suprasellar meningiomas, gliomas and craniopharyngiomas may also be associated with hypopituitarism. Other causes of
hypopituitarism include injury to the pituitary gland following traumatic brain injury or iatrogenically during surgery or cranial irradiation.

Inflammatory conditions of the pituitary may also be responsible for the occurrence of hypopituitarism. The infectious agents that can have been
related to pituitary insufficiency include Mycobacterium tuberculosis and non-mycobacterial agents such as histoplasmosis, syphilis, viruses, and
protozoa. Lymphocytic hypophysitis usually presents in the post-partum period as a mass lesion on magnetic resonance imaging (MRI) due to
infiltration of the pituitary with lymphocytes and plasma cells and is responsive to steroid therapy.

Infiltrative diseases such as hemochromatosis, sarcoidosis, and histiocytosis may be associated with the development of hypopituitarism.

Pituitary apoplexy is a medical emergency and is due to acute ischaemic infarction or hemorrhage of the pituitary gland. Pituitary apoplexy may occur
in the presence of a pituitary adenoma but may also occur in the normal pituitary gland. Sheehan syndrome refers to infarction of the hyperplastic
pituitary gland during pregnancy due to severe blood loss (post-partum hemorrhage). Because of the rich and complex vascular supply pituitary
adenomas have an increased risk of bleeding when compared to other brain tumors.

Congenital absence of the pituitary gland is related to midline and craniofacial defects. Genetic mutations in transcription factors such as HESX1,
PROP1, and Pit-1 can lead to congenital hypopituitarism. Empty Sella syndrome is a rare disorder which is characterized by enlargement or
malformation of the sella turcica resulting in a herniation of the arachnoid membrane into the pituitary fossa dislodging the pituitary to the floor of the
fossa. It is associated with a small or absent pituitary gland. Empty Sella syndrome may be idiopathic or occur secondarily to a treated pituitary tumor,
head trauma, or a condition known as idiopathic intracranial hypertension (pseudotumor cerebri). Kallmann syndrome is a rare genetic condition
associated with an inability to smell (hyposmia/anosmia) and hypogonadotropic hypogonadism (decreased FSH decreased LH, and decreased
testosterone/estradiol) due to a mutation in the Kal1 gene as the commonest genetic abnormality in males.

Epidemiology
There is limited data available regarding the incidence and prevalence of hypopituitarism. One study from Spain reported the annual incidence of
anterior pituitary hormone deficiency to be 4.21 cases per 100,000 population.

History and Physical

It appears that that 75% of the pituitary needs to be damaged to result in hypopituitarism. Clinical features of hypopituitarism may be subtle and ill-
defined or severe with the acute presentation. Conditions such as Sheehan’s syndrome/pituitary apoplexy, pituitary infection, hypophysitis and
traumatic brain injury present with acute findings. [4][5][6]

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Presenting signs and symptoms may be linked to that of a deficiency of pituitary hormone, mass effects in the presence of pituitary tumors, and/or
features of the causative disease. Mass effects include visual field defects known as bitemporal hemianopsia. Visual field defects may also occur
unilaterally. Patients may also present with headaches, secondary to the mass lesions. See table 2 below. It summarises the clinical features of pituitary
hormone deficiencies.

Evaluation
The presence of a secretory pituitary tumor may result in features of hormone excess for the particular hormone produced by a tumor while other
pituitary hormones may be deficient.[7][8][9][10]

Investigations

Laboratory investigations: Initial testing involves baseline levels of pituitary hormones and hormones produced by target hormones. Due to the
variation of hormone levels related to the time of day, season and pulsatile secretion of certain pituitary hormones, baseline levels may not be helpful.
In this instance, dynamic function testing may be performed to confirm biochemical deficiency or excess of a particular pituitary hormone. In dynamic
function testing for the investigation of a hormone deficiency a stimulatory agent that would normally increase secretion of the hormone is given to the
patient and blood levels are measured before administration of the agent and at defined time points after that to determine if there has been an adequate
response to stimulation. See Table 3 Lab findings for pituitary hormone deficiency (per specific hormone).

Insulin Tolerance Test: This is the best provocative test that is used to assess the presence of the deficiency of both GH and cortisol. Following an
overnight fast, baseline samples are obtained for the following hormones cortisol, GH, and glucose. An insulin dose of 0.1 U/kg or 0.05 U/kg is
administered intravenously (IV). Further samples for analysis of the hormones measured in the baseline samples are then taken at several other time
points after administration. Should not be performed in those with cardiac disease or epilepsy. The plasma glucose should fall to 40 mg /dl within 30 to
45 minutes or by 50% of baseline. The test is terminated by giving IV dextrose and assessing the patient's status for at least 90 minutes. A
normal/adequate response is indicated by a cortisol of more than 20 ug/dL and GH more than 5 ng/mL to 10 ng/mL.

Modern combined test: Patient is given GHRH, CRH, GnRH, and TRH as the provocative stimuli and GH, TSH, ACTH, Cortisol, LH, and FSH are
measured at baseline and at specified time intervals after that. Doses of each stimulating hormone are as follows GHRH (1.0 ug/kg); CRH (1.0 ug/Kg);
GnRH (100 ug) and TRH (200 ug). However, this testing is rarely required.

Radiological investigations: Imaging studies of the pituitary using magnetic resonance imaging (MRI) with gadolinium enhancement be used to
visualize the pituitary, in particular, to detect the presence of a mass lesion. Visual field defects need to be assessed if a pituitary mass is the cause of
the hypopituitarism.

Treatment / Management
Management is dependent on the cause of hypopituitarism. Initial treatment is to address the underlying cause of hypopituitarism. Mass lesions may be
removed surgically and other medical conditions treated accordingly. Many patients may require hormone replacement therapy.

ACTH deficit: Corticosteroid replacement should be initiated before replacement of thyroid hormone to avoid precipitating an adrenal crisis.
Hydrocortisone at a dose of 10 mg to 20 mg in the morning and 5 mg to 10 mg in the evening. Prednisone may also be used.

Increased dosages of corticosteroids are given during periods of stress and during surgery and in pregnancy

TSH deficit: Thyroid hormone (L-thyroxine) replacement, in particular for the elderly and those with the cardiac disease It is important to start with a
low dose of 25 ug/daily and the up-titrate as required regarding biochemical findings and clinical signs and symptoms.

FSH/LH deficit: In secondary hypogonadism, testosterone can be delivered by gel, patch, or intramuscular (IM) injections every 2 weeks with a careful
monitoring of prostate-specific antigen (PSA) and Testosterone levels.

In women: estrogen/progesterone hormone replacement therapy via oral, intramuscular or transdermal routes can be given.

If fertility is desired, then one starts off with human chorionic gonadotropin (HCG) to augment testosterone levels and improve semen quality. If this is
not successful after a 1-year, consider human menopausal gonadotropin (HMG)/recombinant FSH concomitant therapy to enhance fertility further

Growth hormone deficit: Unlike in children with short stature due to GH deficiency, the role of GH replacement in the treatment of adult GH
deficiency has not been well established. Synthetic growth hormone replacement is used for somatotrophin. Replacement therapy is titrated against
IGF1 levels. The goal of treatment is to ensure that adult height is obtained. Further evaluation is made post-puberty to determine whether GH
replacement should continue into adulthood.

ADH deficit: Replacement of ADH with intranasal desmopressin (synthetic vasopressin) helps stabilize water balance and polyuria.

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Enhancing Healthcare Team Outcomes

The diagnosis and management of hypopituitarism is done with an interprofessional team that consists of a neurosurgeon, endocrinologist, pathologist,
radiologist, primary care provider, nurse practitioner, and an ophthalmologist. Management is dependent on the cause of hypopituitarism. Initial
treatment is to address the underlying cause of hypopituitarism. Mass lesions may be removed surgically and other medical conditions treated
accordingly. Many patients may require hormone replacement therapy. The outcome in most patients with hypopituitarism are good but those who
have a neurological deficit but continue to have partial deficits even after treatment. [1][11][12](Level V)

Questions
To access free multiple choice questions on this topic, click here.

Figure
Hypopituitariams, Pituitary Hormone Chart. Contributed by Verena Gounden

References
1. Sun S, Liu A, Zhang Y. Long-Term Follow-Up Studies of Gamma Knife Radiosurgery for Postsurgical Nonfunctioning Pituitary Adenomas. World
Neurosurg. 2019 Jan 17; [PubMed: 30660894]
2. Thompson CJ, Costello RW, Crowley RK. Management of hypothalamic disease in patients with craniopharyngioma. Clin. Endocrinol. (Oxf).
2019 Apr;90(4):506-516. [PubMed: 30614015]
3. Qiao N. Excess mortality after craniopharyngioma treatment: are we making progress? Endocrine. 2019 Apr;64(1):31-37. [PubMed: 30569259]
4. Abdelmannan D, Aron DC. Incidentally discovered pituitary masses: pituitary incidentalomas. Expert Rev Endocrinol Metab. 2010 Mar;5(2):253-
264. [PubMed: 30764049]
5. Arnaldi G, Cardinaletti M, Trementino L, Tirabassi G, Boscaro M. Pituitary-directed medical treatment of Cushing's disease. Expert Rev
Endocrinol Metab. 2009 May;4(3):263-272. [PubMed: 30743797]
6. Healy ML, Smith TPP, McKenna TJ. Diagnosis, misdiagnosis and management of hyperprolactinemia. Expert Rev Endocrinol Metab. 2006
Jan;1(1):123-132. [PubMed: 30743775]
7. Lamas C, García-Martínez A, Cámara R, Fajardo-Montanana C, Viguera L, Aranda I. Silent somatotropinomas. Minerva Endocrinol. 2019
Jun;44(2):137-142. [PubMed: 30531696]
8. Tan CL, Hutchinson PJ. A neurosurgical approach to traumatic brain injury and post-traumatic hypopituitarism. Pituitary. 2019 Jun;22(3):332-337.
[PMC free article: PMC6510708] [PubMed: 30483919]
9. Bernabeu I, Aller J, Álvarez-Escolá C, Fajardo-Montañana C, Gálvez-Moreno Á, Guillín-Amarelle C, Sesmilo G. Criteria for diagnosis and
postoperative control of acromegaly, and screening and management of its comorbidities: Expert consensus. Endocrinol Diabetes Nutr. 2018
May;65(5):297-305. [PubMed: 29653911]
10. Delgado-López PD, Pi-Barrio J, Dueñas-Polo MT, Pascual-Llorente M, Gordón-Bolaños MC. Recurrent non-functioning pituitary adenomas: a
review on the new pathological classification, management guidelines and treatment options. Clin Transl Oncol. 2018 Oct;20(10):1233-1245.
[PubMed: 29623588]
11. Zhang Z, Wang P, Feng S, Yu X. Endocrinological Outcomes of Intraoperative MRI-Guided Endoscopic Transsphenoidal Surgery for Non-
Functioning Pituitary Adenoma. Turk Neurosurg. 2019;29(5):635-642. [PubMed: 30649793]
12. Jamshidi AO, Beer-Furlan A, Prevedello DM, Sahyouni R, Elzoghby MA, Safain MG, Carrau RL, Jane JA, Laws ER. A modern series of
subdiaphragmatic craniopharyngiomas. J. Neurosurg. 2018 Oct 26;131(2):526-531. [PubMed: 30485192]

Publication Details

Author Information

Authors

Verena Gounden1; Ishwarlal Jialal2.

A liations

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1
University of KwaZulu Natal
2
VA MEDICAL CENTER, MATHER, CA

Publication History

Last Update: July 28, 2019.

Copyright
Copyright © 2020, StatPearls Publishing LLC.

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NLM Citation
Gounden V, Jialal I. Hypopituitarism (Panhypopituitarism) [Updated 2019 Jul 28]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-.

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