Descriptions of Each Silent Pituitary Adenoma Subtype

Silent Subtype 3 Adenomas

Silent subtype 3 adenomas is a rare plurihormonal tumor that have
immunoreactivities for more than one pituitary hormone, which are not related
to the typical cytogenesis and development of the anterior pituitary, but are
nonfunctioning clinicallyi. However, they exclude the combinations of (1) GH,
PRL and TSH, and (2) FSH and LH, because these two combinations are already
commonly found in GH-secreting adenomas and gonadotropin-secreting
adenomas, respectively. These tumors have spheridia, which are characteristic
ultrastructual appearance with intranuclear inclusionsii.
These tumors occur both in males and females and have equal
incidences1(buku). Silent subtype 3 adenomas tend to be more aggressive clinically
and have recurred in 31% patients in one studyiii. Another study found that 23%
cases had postoperative recurrencesiv.

Silent Prolactinomas
Prolactinomas have the prevalence of 45–50 per million, which makes it
the most common secretory pituitary adenomav. However, the presence of a
prolactinoma is rarely unaccompanied with clinical signs and symptoms (sama
kyk reference ivan no. 1).

Silent TSH-Secreting Adenomas

TSH-secreting adenomas comprises 0.2-2.8% of all pituitary adenomasvi.
A study showed that from 12 TSH-secreting adenomas, 1/3 of patients did not
show signs of clinical hyperthyroidism. One patient showed normal thyroid
function tests, two patients showed elevated TSH with normal T4 levels, and the
last patient showed normal TSH levels with high T3 and T4 levelsvii.

Silent Gonadotropin-Secreting Adenomas

These tumors are defined as clinically nonfunctioning adenomas which
immunohistochemistry shows FSH, LH and/or alpha subunit but do not secrete
these hormontes, or if secreted do not cause hormone-related clinical
symptomsviii.
Silent gonadotroph adenomas appear to be the most common type of
clinically nonfunction adenomas, presenting 10% of all pituitary adenomas
(sama kyk reference ivan no. 1).

Silent Corticosteroid-Secreting Adenomas

20% of silent corticotroph adenomas do not manifest biochemical or
clinical signs of hypercortisolism(sama kyk reference ivan no. 1). Some SCAs may
cause elevated ACTH levels with normal cortisol levels. (sama kyk reference ivan
no. 1).
Studies report the prevalence of SCAs to be 3-19% of adenomas
preoperatively diagnosed to be nonfunctioning. In the German Registry of
Pituitary Tumors, it is stated 5.5% of silent adenomas were SCAs. Type II
adenoma (sparsely granulated) were more common at 4.4%, and type I (densely
granulated) had 1.1% prevalence (sama kyk reference ivan no. 8).
Prognosis of SCAs
A cohort study of 25 SCAs showed that these tumors have a high
recurrence rate of 63% compared to 38% in non-functioning adenomas. SCAs
also recurred five years earlier than non-functioning adenoma, and de novo
recurrences are seen more commonly in patients with SCAix. However another
study showed otherwisex. SCAs may also rarely transform into functional
corticotroph adenomas along the natural history of the diseasexi,xii,xiii.

i Pathology and Genetics of Tumours of Endocrine Organs

ii Horvath E, Lloyd RV, Kovacs K, et al. Plurihormonal adenoma. DeLellis RA,
Lloyd RV, Heitz PU, Eng C, eds. 2004 World Health Organization Classification of
Tumours. Pathology and Genetics of Tumours of Endocrine Organs. Lyon, France:
IARC Press; 2004. 35.
iii Horvath E, Kovacs K, Smyth HS, Cusimano M, Singer W. Silent adenoma subtype

3 of the pituitary--immunohistochemical and ultrastructural classification: a

review of 29 cases. Ultrastruct Pathol. 2005;6:511–524.
iv Erickson D, Scheithauer B, Atkinson J, Horvath E, Kovacs K, Lloyd RV, Young

WF., Jr Silent subtype 3 pituitary adenoma: a clinicopathologic analysis of the

Mayo Clinic experience. Clin Endocrinol (Oxf) 2009;1:92–99.
v Fernandez A, Karavitaki N, Wass JA. Prevalence of pituitary adenomas: a

community-based, cross-sectional study in Banbury (Oxfordshire, UK) Clin

Endocrinol (Oxf) 2010;3:377–382.
vi Beckers A, Abs R, Mahler C, Vandalem JL, Pirens G, Hennen G, Stevenaert A.

Thyrotropin-secreting pituitary adenomas: report of seven cases. J Clin

Endocrinol Metab. 1991;2:477–483.
vii Bertholon-Gregoire M, Trouillas J, Guigard MP, Loras B, Tourniaire J. Mono-

and plurihormonal thyrotropic pituitary adenomas: pathological, hormonal and

clinical studies in 12 patients . Eur J Endocrinol. 1999;6:519–527.
viii Greenman Y, Stern N. Non-functioning pituitary adenomas. Best Pract Res Clin

Endocrinol Metab. 2009;5:625–638.

ix Cooper O, Ben-Shlomo A, Bonert V, Bannykh S, Mirocha J, Melmed S. Silent

corticogonadotroph adenomas: clinical and cellular characteristics and long-

term outcomes. Horm Cancer. 2010;2:80–92.
x Bradley KJ, Wass JA, Turner HE. Non-functioning pituitary adenomas with

positive immunoreactivity for ACTH behave more aggressively than ACTH

immunonegative tumours but do not recur more frequently. Clin Endocrinol
(Oxf) 2003;1:59–64.
xi Baldeweg SE, Pollock JR, Powell M, Ahlquist J. A spectrum of behaviour in silent

corticotroph pituitary adenomas. Br J Neurosurg. 2005;1:38–42.

xii Yokoyama S, Kawahara Y, Sano T, Nakayama M, Kitajima S, Kuratsu J. A case of

non-functioning pituitary adenoma with Cushing's syndrome upon recurrence.

Neuropathology. 2001;4:288–293.
xiii Psaras T, Honegger J, Buslei R, Saeger W, Klein D, Capper D, Mittelbronn M.

Atypical type II silent corticotrophic adenoma developing into Cushing's disease

upon second recurrence. Exp Clin Endocrinol Diabetes. 2007;9:610–615.