Syndromes of Pituitary Hormone Excess

1. Syndromes of Pituitary Hormone Excess Dr Mohamed Abdel WahabEzzat Lecturer of Internal Medicine and Cardiology Faculty of Medicine Sohag University

2. Growth Hormone • Stimulus = Tissue growth/ repair • Hypothalamus releases GHRH • Anterior Pituitary releases GH •  Protein synthesis, growth, etc. • GH and release of somatostatin shuts off GHRH and GH release

3. Normal growth • There are factors other than GH involved in linear growth in the human. • Genetic factors. Children of two short parents will probably be short and vice versa. • Nutritional factors. Adequate nutrients must be available. Impaired growth can result from inadequate dietary intake or small-bowel disease (e.g. coeliac disease).

4. Normal growth (cont.) • General health. Any serious systemic disease in childhood is likely to reduce growth (e.g. renal failure). • Intrauterine growth retardation. These infants often grow poorly in the long term, while infant s with simple prematurity usually catch up. There is some evidence that low birthweight may predispose to hypertension, diabetes and other health problems in later adult life.

5. Normal growth (cont.) • Emotional deprivation and psychological factors. These can impair growth by complex, poorly understood mechanisms, probably involving temporarily decreased GH secretion.

6. TALL STATURE • The most common causes are hereditary (two tall parents!), idiopathic (constitutional) or early development. It can occasionally be due to hyperthyroidism. • Other causes include chromosomal abnormalities (e.g. Klinefelter's syndrome, Marfan's syndrome) or metabolic abnormalities. • GH excess is a very rare cause and is usually clinically apparent.

7. What happens with excess GH?

8. GH as Juvenile

9. GH as an Adult

12. GH = pituitary dwarfism

13. 1. Acromegaly and Gigantism • Caused by excess growth hormone secretion usually from a pituitary macroadenoma. • Rare causes; ectopic production of GHRH (e.g. from a pancreatic tumor). • If acquired before epiphyseal closure gigantism, in adult life Acromegaly. • GH acts directly on some tissues, but most of its actions are mediated through stimulation of secretion of IGF-1 and IGF-BP from liver.

14. Clinical features of Acromegaly • Soft tissue changes; • Skin; thickening, increased sweating and sebum production • Enlargement of lips, nose & tongue. • Myopathy, arthropathy. • Carpal tunnel syndrome. • Visceromegaly.

15. Clinical features of Acromegaly • Bone changes: • Large hands, large feet. • Growth of lower jaw (prognathism) • Skull; prominent supraorbital ridges, large frontal sinuses. • Kyphosis, osteoarthritis. • Metabolic changes: • Glucose intolerance (25%), diabetes (10%). • Hypertension. • Long term complications; athertomatous diseases.

16. Investigations of Acromegaly • GH level; may exclude acromegaly if undetectable. (normal adult level <1m U/L except during stress) • Measuring GH during a glucose tolerance test. Failure of suppression or sometimes paradoxical rise occur. • IGF-1 levels; almost always high. • Serum prolactin levels. • Investigations of space occupying lesions.

17. Treatment • Aim of treatment To achieve a mean GH level below 5mU/L which has been shown to reduce mortality to normal levels. • Causes of mortality: Coronary heart diseases, heart failure, hypertension-related causes and increased risk of neoplasms. • Concurrent diabetes or hypertension should treated conventionally.

18. Lines of Treatment • Surgical Trans-sphenoidal or trans-frontal surgery. • Radiotherapy External radiotherapy usually used to shrink tumor size after pituitary surgery fails.

19. Lines of Treatment (cont.) • Medical • Octreotide or lanreotide; Synthetic analogue of somatostatin. Lowers GH levels but doesn’t shrink tumor size. Given as subcutaneous injections 2-3 times/day. New long acting preparations given monthly. Side effects: increased incidence of gall stones.

20. Lines of Treatment (cont.) Medical • Dopamine agonists; help shrinking tumor size, especially in cases with mixed GH and prolactin- producing adenomas. • GH antagonists Pegvisomant; GH receptor antagonist

21. 2. Hyperprolactinemia • Causes • Physiological: - Stress, Pregnancy or lactation. • Pathological: - Disconnection hyperprolactinemia - Prolactinoma or Mixed pituitary adenoma - Primary hypothyroidism - Hypothalamic disease - Ectopic source

22. Causes (cont.) • Drugs: - Dopamine antagonist as antidepressants or anti-emetics. - dopamine depleting drugs as reserpine or methyldopa. - Estrogen therapy as contraceptive pills.

23. Hyperprolactinemia; clinical features • Cardinal features are galactorrhea and hypogonadism. • In women; secondary amenorrhea, oligomenorrhea or menorrhagia, unovulation and infertility. • In men; decreased libido, erectile dysfunction and lethargy. • Delayed or arrested puberty in the prepubertal patient. • Other symptoms or signs of pituitary tumors.

24. Hyperprolactinemia; Investigations • S. prolactin; upper limit is 360 mU/l. • Stress or drugs can increase serum levels to 1000 mU/l. • Levels above 4000 are highly suggestive of prolactinoma. • Patients with prolactin excess should have tests for thyroid dysfuction, gonadal dysfunction, hypopituitarism, tests for associated GH excess, visual field defects and pituitary imaging.

25. Hyperprolactinemia; Management • Medical: - In almost all cases, dopamine agonist therapy will normalize S. prolactin level. It also shrink the majority of macroadenoma. - The treatment is likely to be long term in the majority of patients. - Patients with microadenoma are advised to stop therapy as soon as pregnancy is confirmed. - drugs in use; Bromocriptin 2.5-15 mg/ day others; cabergoline; 250-1000µg/week

26. Hyperprolactinemia; Management • Surgical - Usually medical treatment is sufficient unless the macroadenoma is cystic. Or if the patient is intolerant to dopamine agonists. • Radiotherapy sometime required to prevent re-growth after dopamine agonists are stopped.