Hypopituitarism (Simmonds' disease)


Look at this patient.



· In a male, the frequency of shaving, impotence.

· In a female, postpartum haemorrhage, amenorrhoea.

· History of radiation (e.g. proton-beam radiation) - causes hypopituitarism primarily

because of its effects on hypothalamic function, whereas high-dose radiation can

directly affect the pituitary.


· Patient is pale; the skin is soft.

· Paucity of axillary and pubic hair.

· Atrophy of breast (in females).

· Examine the blood pressure for postural hypotension.

· Check visual fields: bitemporal hemianopia may be present.

· Examine the fundus for optic atrophy.

Proceed as follows:

Tell the examiner that you would like to examine the external genitalia for

hypo-gonadism (small testes).


This patient has pale soft skin and absence of axillary hair with atrophied breasts

(lesion) due to hypopituitarism (functional status) secondary to postpartum

necrosis (aetiology).


Mention a few causes of hypopituitarism.

· Iatrogenic - from surgical removal of the pituitary or irradiation.

· Chromophobe adenoma (particularly in males).

· Postpartum pituitary necrosis in females - known as Sheehan's syndrome.

Rare causes

· Craniopharyngioma.

· Metastatic tumours, granulomas (TB, sarcoid, haemochromatosis, histiocytosis X).

How would you assess such a patient?

· FBC for normochromic normocytic anaemia.

· Urea and electrolytes for hyponatraemia due to dilution. Hyperkalaemia does not

usually occur because aldosterone production is not affected.

· Measurement of pituitary hormone levels (ACTH, TSH, luteinizing hormone (LH),

growth hormone, prolactin).

· Measurement of target organ secretion (T4, T3, serum cortisol, testosterone,

oestrogen and progesterone levels).

· Pituitary stimulation tests:

-Thyrotrophin-releasing hormone (TRH) stimulation tests. -Tetracosactide

(Synacthen) tests. -Insulinhypoglycaemia test.

-Luteinizing hormone releasing hormone (LHRH) tests.

· Skull radiography.

· MRI provides the best image of parasellar lesions. The posterior pituitary usually

has a high-intensity signal on sagittal MRI that is absent in central diabetes


· Assessment of visual fields (formal perimetry).

In what order do the hormone secretions generally fail?

In general, growth hormone, follicle-stimulating hormone (FSH) and LH secretions

become deficient early, followed by TSH and ACTH. Last of all, antidiuretic

hormone (ADH) secretions diminish and fail.

How would you treat such patients?

The mainstay of therapy is lifetime replacement of end-organ hormone deficiencies

(thyroid, adrenal and gonads).

Does hypopituitarism affect life expectancy?

Even when hormonal replacement therapy (adrenal, gonadal and thyroid) is carried

out in an adequate manner, there is a two-fold risk of death in patients with

hypo-pituitarism (J Clin Endocrinol Metab 1996; 81:1169-72). It has been

suggested that this is due to untreated growth hormone deficiency.


What is the Houssay phenomenon?

Houssay showed that diabetes of pancreatectomized dogs improved after

hypophysectomy. A diminishing requirement of insulin by diabetics may be a sign

of hypopituitarism with diminished secretion of growth hormone and ACTH (and

thus corticosteroids). Similarly, diabetes due to acromegaly may improve with

pituitary surgery or octreotide therapy.

Morris Simmonds of Hamburg described this condition in 1914.

Bernardo Alberto Houssay (1889-1971), an Argentinian physiologist in Buenos Aires,

was awarded the Nobel Prize for his discovery of the part played by the hormone

of the anterior pituitary lobe in the metabolism of sugar. The other half of the Nobel

Prize was awarded to Carl and Gerty Cori of St Louis, Missouri., USA, who were

awarded the prize for their discovery of the course of the catalytic conversion of