Two pituitary axes are covered here: loss of the adrenocorticotropic hormone (ACTH) axis, which controls cortisol production by the adrenal cortex, causes secondary hypocortisolism, and loss of the gonadotropin axis, the luteinizing hormone (LH) and follicle-stimulating hormone (FSH) that stimulate the gonads, causes hypogonadotropic hypogonadism.
ACTH deficiency
The zona fasciculata and zona reticularis of the adrenal cortex, which produce cortisol and androgens respectively, are ACTH-dependent for the production and secretion of these hormones. When ACTH falls, so does cortisol, and the result is secondary hypocortisolism, or secondary adrenal insufficiency, secondary because the failure lies in the pituitary rather than in the adrenal gland. It manifests as fatigue and weakness, anorexia, nausea and vomiting, occasional hypoglycaemia, and a preserved level of mineralocorticoid. Because aldosterone, the adrenal mineralocorticoid, is preserved, the hyperkalaemia that is common in primary adrenal insufficiency is not seen. Two findings point instead to primary hypocortisolism, in which the adrenal gland itself fails: hyperpigmentation, and a reduced level of mineralocorticoids.
The main causes of secondary hypocortisolism, or ACTH deficiency, are iatrogenic, after withdrawal of glucocorticoids, when the hypothalamus and pituitary need time to reactivate their production of the adrenal-related hormones; mass effects; and post-surgical damage.
Gonadotropin deficiency
Hypogonadism is the most common presenting feature of adult hypopituitarism, even when other pituitary hormones are affected. Low gonadotropin-releasing hormone (GnRH), the hypothalamic hormone that stimulates LH and FSH release, whether from a mass effect or from lesions of the hypothalamus or pituitary, leads to low production of steroid hormones, and hyperprolactinaemia independently causes hypogonadotropic hypogonadism, so it must always be considered alongside.
The causes of a hypogonadotropic state include inherited disorders such as Kallmann syndrome, GnRH receptor mutations, LHβ and FSHβ subunit mutations, stress, severe exercise, anorexia nervosa and starvation, and idiopathic causes.
The presentation differs by sex and age. In premenopausal women, lower follicular activity produces oligomenorrhoea and amenorrhoea, together with infertility, reduced vaginal secretion, decreased libido, breast atrophy and osteoporosis. In men, the picture is decreased libido and potency, infertility, decreased muscle mass and weakness, soft testes, reduced beard and body hair growth, and osteoporosis.
Because gonadotropin release is pulsatile, a pooled sample is suggested for testing, and in men sperm counts will be decreased. The GnRH stimulation test gives intravenous GnRH and observes the response: a normal increase of FSH and LH places the problem in the hypothalamus or stalk, whereas an abnormal response cannot distinguish a pituitary from a hypothalamic cause.