Acromegaly

Definition. Acromegaly is a syndrome of excessive secretion of growth hormone. In children
this is called gigantism. Acromegaly is an insidious, chronic debilitating disease associated with
bony and soft tissue overgrowth.
Etiology. Acromegaly is caused by pituitary adenomas, usually a macroadenoma in 75% of the
cases that produce growth hormone (GH). Rarely ectopic tumors can produce GH or growth
hormone releasing hormone (GHRH) and cause this syndrome.
Clinical Findings. Growth hormone excess occurs most frequently between the third and fifth
decades of life.
Various skeletal and soft tissue changes occur. Enlargement of the hands and feet, coarsening of
facial features, and thickened skin folds occur. There is also enlargement of the nose and
mandible (prognathism and separation of teeth), sometimes causing underbite.
The internal organs are enlarged, including heart, lung, spleen, liver, and kidneys. Interstitial
edema, osteoarthritis, and entrapment netrropathy (carpal tunnel syndrome) are seen.
Metabolic changes include impaired glucose tolerance (80%) and diabetes (13-20%).
Hypertension is seen in one third of patients. Headaches and visual field loss can also occur.
Diagnosis. Patients with acromegaly have symptoms for an average of 9 years before the diagnosis
is made.
Screening test involves the measurement of GH after 100 g of glucose is given orally; this test is
positive if GH remains high (>5 ng/mL) and suggests acromegaly. Normally a glucose load
should suppress levels of GH.
Measurement of insulin-like growth factor (IGF) or somatomedin (SMF) correlates with disease
activity.
Radiologic studies such as computed tomography (CT) and magnetic resonance imaging
(MRI) are used to localize the tumor but should be done only after GH excess is documented
biochemically.
Management. The objectives in managing patients with acromegaly are to decrease GH levels to
normal, stabilize or decrease tumor size, and preserve norinal pituitary function. Bromocriptine
is a dopamine agonist that can be used to treat acromegaly; one fourth of patients with
acromegaly respond to bromocriptine.
Octreotide is a somatostatin analog that reduces GH values in two thirds ofpatients and causes partial
tumor regression in 20-50% of patients.
Transphenoidal surgery provides a rapid response, but hypopituitarism can result in 10-20% of
patients. Radiotherapy results in slow resolution of disease and hypopituitarism in 20% of patients.
Complications. Complications of acromegaly can arise from pressure of the tumor on the
surrounding structures or rupture of the tumor into the brain or sinuses. Other complications
include cardiac failure (most common cause of death in acromegaly), diabetes mellitus, cord compression,
and visual field defects.

DISEASES OF THE PITUITARY GLAND

DISEASES OF THE PITUITARY GLAND

The pituitary is surrounded by the sphenoid bone and covered by the sellar diaphragm, an extension from the dura mater. It lies in the sella turcica near the hypothalamus and optic chiasm.
The pituitary is divided into two lobes—the adenohypophysis or anterior lobe, which constitutes 80% of the pituitary; and the neurohypophysis or posterior lobe, which is the storage site for hormones produced by the neurosecretory neurons (supraoptic and paraventricular nuclei within the hypothalamus). The two hormones stored in the posterior lobe are ADH (antidiuretic hormone or vasopressin) and oxytocin.
There is a very close relationship between the hypothalamus and the pituitary; The hypothalamus regulates the release of hormones from the anterior pituitary by different hypothalamic releasing and inhibiting hormones (hypothalamic—pituitary axis).

DISEASES OF THE ANTERIOR PITUITARY
Syndromes causing excess production of hormones usually arise from only a single cell type.
Microadenomas are defined as those <1>1 cm in diameter and are associated with panhypopituitarism and visual symptoms.

Prolactin 50—60%
Growth hormone 15—20%
ACTH 10-15%
Gonadotroph 10—15%

Hyperprolactinemia
A 32-year-old woman comes to your office because she has noticed milk- like discharge from her breasts the past 4 weeks. The examination reveals galactorrhea but is otherwise normal. How should you approach this case?
Definition. Excess prolactin secretion is a common clinical problem in women and causes the syndrome of galactorrhea-amenorrhea. The amenorrhea appears to be caused by inhibition of hypothalamic release of luteinizing hormone releasing hormone (LHRH) with a decrease in luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion.
Prolactin inhibits the LH surge that causes ovulation. The LH/FSH-producing cells are not destroyed, just suppressed. Although hyperprolactmemia is also seen in men, gynecomastia and especially galactorrhea are very rare.
Etiology. Hyperprolactinemia can be seen in natural physiologic states such as pregnancy,
early nursing, hypoglycemia, seizure, exercise, stress, sleep, cirrhosis, nipple stimulation, and chronic renal failure (due to PRL clearance).
Autonomous production of prolactin occurs with pituitary adenomas; these so-called prolactinomas are the most common functioning pituitary adenomas, accounting for 60% of all pituitary tumors. They are usually microadenomas when they occur in women and macroadenomas in men, usually presenting with visual field deficits, etc. Damage to the pituitary stalk increases prolactin release by blocking dopamine transport from hypothalamus (stalk effect). Examples are tumors, such as craniopharyngioma, meningioma, and dysgerminoma; empty sella; and trauma.
Hyperprolactinemia can also occur with decreased inhibitory action of dopamine. This occurs with the use of drugs that block dopamine synthesis (phenothiazines, metoclopramide) and dopamine-depleting agents (cr-methyldopa, reserpine). Tricyclic antidepressants, narcotics, cocaine, SSRIs, and risperidone can also cause increased prolactin.
Stimuli that overcome the normal dopamine inhibition can also lead to hyperprolactinemia.
An example of this is primary hypothyroidism (resulting in an increase in thyrotropin-releasing hormone [TRH]) and subsequently an increase in prolactin release.
Check the TSH
Clinical. Hyperprolactinemia presents with galactorrhea, menstrual abnormalities amenorrhea/oligomenorrhea, osteoporosis and osteopenia in long-standing cases, infertffity and gynecomastia in women; men present with hypogonadism, erectile dysfunction, decreased libido, gynecomostia in men and infertility. Men do not get galactorrhea. Women are detected earlier because of menstrual symptoms. Hence, microadenomas are more common in women.
Diagnosis. Always exclude states such as pregnancy; lactation, hypothyroidism and medications before starting the work-up of hyperprolactinemia. Prolactinomas may co-secrete growth hormone.
Prolactin levels >100 ng/mL suggest probable pituitary adenoma. Prolactin level should be commensurate with tumor size.
Management. For prolactinomas, initially treat with cabergoline or bromocriptine (a dopamine
agonist), which reduce prolactin levels in almost all hyperprolactinemic patients. Dopamine
normally inhibits prolactin release. Surgery is reserved only for adenomas not responsive to
cabergoline or bromocriptine, or if the tumor is associated with significant compressive neu-
rologic effects. Surgery is more effective for microadenomas than macroadenomas. Only 30%
of macroadenomas can be successfully resected (long-term recurrence >50% in macroad-
enoma). About 90% of patients treated with cabergoline have a drop in prolactin to <10% of
pretreatment levels. Radiation is used if drug therapy and surgery are ineffective.