(a bit of) Endocrine

1. (a bit of) Endocrine Dr Alex Smith 12th March 2013

2. Overview • What this will cover • Cases: • Thyroid disease • Pituitary disease • Adrenal disease • A few quiz questions (if time allows) • Eponymous syndromes game (woo) • What I won’t cover • Diabetes and DM emergencies

3. Case 1 – a lump in the neck • A 27 year old woman presented to her GP with an increase in the size of a longstanding lump in her neck. • She had first noticed it four years ago, as a small right sided lump, but in recent months it had increased in size to cause obvious asymmetry.

4. Neck Lumps • How do you assess? • Differential Diagnosis?

5. Case 1 • On examination, she had a single well defined lump in the right anterior triangle, extending down to her clavicle. She was clinically euthyroid and thyroid function tests were unremarkable.

6. Case 1 • What is the differential diagnosis in a young woman with these symptoms? • In a young euthyroid patient, a neoplastic thyroid lesion should be excluded first. • What symptoms would require urgent investigation? • Local symptoms such as voice changes, dysphagia • Cervical lymphadenopathy • Associated red flags e.g. Weight loss • History of rapid enlargement • Stridor • Any nodule in a child

7. Case 1 • What is the diagnostic investigation of choice? • Fine needle aspiration is the investigation of choice for a definitive histological diagnosis. • What other investigations might add to the clinical picture? • Ultrasound of the neck will help localise the anatomical origin

8. Neck Lumps • Congenital • Branchial cyst • Cystic hygroma • Parotid tumour • Carotid body tumour • Endemic • Thyroid: • Thyroiditis • Hashimoto’s disease • Physiological • Multinodular goitre • Single thyroid lump • Cyst • Adenoma • Malignancy (papillary, follicular, medullary, anaplastic, lymphoma) • Smooth toxic goitre • Graves’ disease • Discrete nodule in multinodular goitre • Goitrogens

9. Thyroid Ca • Thyroid lymphomas • Thyroid lymphomas are almost always non-Hodgkin lymphomas, representing 4 to 10% of thyroid malignancies. • Mainly women over 50 are affected and they often have Hashimoto's thyroiditis. • Patients usually present with a rapidly growing mass in the neck, which may cause symptoms of obstruction such as dyspnoea and dysphagia. • Thyroid lymphoma arises in a pre-existing chronic thyroiditis with subclinical or overt hypothyroidism in 70 to 80%. • The prognosis depends on the stage of the disease at diagnosis. • The 5-year survival rate ranges from 89% in early disease to 5% in disseminated disease. • Hurthle cell carcinoma • About 2 to 5% of thyroid cancers are Hurthle cell carcinoma.6 • There is a female preponderance - mainly in their 40s. • They are composed of 75 to 100% Hurthle cells. • It is impossible to distinguish benign from malignant tumours on fine needle aspiration (FNA). • They do not take up iodine nor respond to TSH. • 5-year survival rate is around 50%. • Anaplastic carcinoma • This represents less than 2% of thyroid cancers. • Women are affected more often than men. • It is found aged 50 to 60. • Half have metastases at presentation and prognosis is poor. Papillary thyroid carcinoma (PTC) • This is the commonest form of thyroid cancer. • It usually presents between 35 and 40 years of age and is 3 times more common in women. • It tends to spread locally in the neck, compressing the trachea and possibly involving the recurrent laryngeal nerve. • It can metastasise to lung and bone. Follicular thyroid carcinoma (FTC) • This is the second commonest form of thyroid cancer at about 10%. • It tends to occur in areas of low iodine. • It is 3 times as common in women and tends to strike between 30 and 60 years of age. • It may infiltrate the neck as does papillary carcinoma but it has a greater propensity to metastasise to lung and bones. Medullary cell carcinoma • This is about 5% of thyroid cancers. • About 25% of patients give a family history. • Female prepronderance is less marked. • Prophylactic thyroidectomy is advocated for those at risk. • The familial form is discussed in the article Multiple Endocrine Neoplasia Type 2 (MEN2).

10. Case 2 - thirst • 52 yo overweight man presented to his GP with a 4 week history of increasing thirst and polyuria. In addition he was also increasingly tired, constipated and suffering from low mood. • Initial thoughts?

11. Case 2 - thirst • Urinalysis NAD • BM 6.2 • Baseline bloods reveal: • Adj Calcium 2.8

12. Parathyroid • Hyperparathyroid and malignancy together make up 90% of the causes of hypercalcaemia • Primary hyperparathyroidism is the commonest single cause • Investigations • Serum PTH and calcium. • Ultrasound, CT,MRI, isotope MIBI scanning to localise site of the disease. • Management: • Acutely: IV fluids. In severe hypercalcaemia, bisphosphonates can help reduce bone turnover and decrease calcium. • The definitive treatment for parathyroid causes is surgical exploration of the neck.

13. Effects of PTH

14. Case 3 • A 34 year old man was admitted to AMU with a history of headache and vomiting. • He had been experiencing neck pain for the preceding 4 months; his headache had developed gradually over this time but had worsened over the past two weeks. The headache was over the frontal area of the skull radiating to the neck. • The headache was not related to time of day. He also described some pain over his left eye. • He had a two week history of vomiting associated with the headache, but no photophobia.

15. Case 3 • O/e: Temperature 36.8°C RR 15 HR 85, BP 125/65 mmHg • Neuro: • Papilloedema • Bitemporalhemianopia. • Impression?

16. Case 3 • Blood tests initially showed • Hb 15.5 • WCC 12.0 • Neutrophils 10.1 • Platelets 225 • Urea 5.3 • Na 136 • K 3.7 • HCO3 27

17. The MRI scan shows a very large enhancing mass centred on the suprasellar region, markedly expanding the sella and with lateral extension into both cavernous sinuses. The optic chiasm cannot be identified but is presumably grossly elevated and compressed. The differential diagnoses that must be considered are pituitary adenoma, craniopharyngioma, chordoma, and meningioma

18. Case 3 - bloods • Prolactin: 35190 pmol/l (207-725) • 8 am: cortisol concentration of 75 nmol/l • TSH 0.6 mIU/l (0.5-4.7) • Free thyroxine 11 pmol/l (9-24) • FSH 3.3 IU/l (1-7) • LH 1.4 IU/l (1-8) • Testosterone 1.9 nmol/l (8-27)

19. Case 3: Treatment What treatment should be started? • Dopamine agonist therapy (bromocriptine, cabergoline, or quinagolide) ...(dopamine inhibits prolactin release) • Complications: nausea and vomiting, headache and mood alteration, hypotension.

20. Pituitary tumours • Symptoms from: • Excessive hormone production • Local effects of the tumour • Inadequate hormone production by the remaining pituitary gland • Origins: • Non-functioning adenomas • Prolactinomas • Growth hormone (GH)-secreting • ACTH-secreting • Thyroid-stimulating hormone-secreting • Leutinising hormone/follicle-stimulating hormone (LH/FSH)-secreting tumours

21. Case 4 – tired all the time • A 77 yo man presented to his GP for annual blood pressure check • Increasingly tired over last few months. • Several episodes of dizziness on climbing stairs • One admission to A&E for a fall • o/e Thin, lightly tanned. Nil else specific. • BP 100/76 Pulse 68

22. Case 4 - investigations • Hb 13.5 • Na 127 • K 5.0 • Cr 120 • Urea 7 • Random cortisol - 250nmol/L

23. Case 4 • Short Synacthen tests: • Adminstration of synthetic ACTH, and monitoring cortisol response. • 0 min. - baseline blood for cortisol; follow by 250 micrograms synacthen® IV/IM • 30 and 60 minutes: measure cortisol level • Cortisol levels > 550nmol/L indicates a normal response. • Peak cortisol levels < 550nmol/L indicate hypoadrenalism (primary or secondary)

24. The Adrenals

25. Addison’s Disease • Adrenal insufficiency, mostly due to autoimmune pathology in developed countries. It involves atrophy of the entire adrenal cortex. TB is a major cause globally. • Approximately 80-90% of adrenal tissue in both glands must be affected to destroy adrenal reserve. • Symptoms include: malaise, weight loss, postural hypotension, skin pigmentation, abdominal pain. • Ix:ACTH Usually >50ng/L. If the level is raised, this indicates PRIMARY hypoadrenalism, if it is reduced, SECONDARY hypoadrenalism is likely. • Treatment is for life. Hydrocortisone (synthetic cortisol) andfludrocortisone (synthetic aldosterone). Increased in times of physical stress (e.g. Infection, surgery) to avoid adrenal crisis. • Crisis: hypotension, abdominal pain, circulatory collapse

26. Case 5 – headache • A 39 year old woman was referred to the headache clinic with a 2 year history of episodic headaches, sweating, and palpitations. • The symptoms had intensified over the past 6 months. • Since then she has been experiencing three to four episodes a day, mostly at night, of severe headache, chest tightness, sweating, palpitations, and “churning stomach.” • She had no medical history of note and took no regular drugs.

27. Case 5 continued • O/e • BP 100/80 mmHg -no postural drop • pulse 86 regular. • No associated lymphadenopathy • Other examinations unremarkable.

28. Case 5 continued • All bloods normal • 24 hour urinary catecholamines: • markedly raised noradrenaline (628 nmol/L reference range 0-450) • and adrenaline (722 nmol/L ref 0-100), suggestive of • phaeochromocytoma

29. Case 5 continued • MRI of the adrenals showed a large mass in the right upper quadrant and a small mass in the left adrenal. • Phaeochromocytoma: a neuroendocrine tumour of the medulla of the adrenal glands (originating in the chromaffin cells)

30. Case 5 continued • Management of phaeochromocytoma includes • α adrenoceptor blockade (with/without β adrenoceptor blockade) • surgical resection • Also associated with thyroid nodules: as part of multiple endocrine neoplasia syndrome type 2 (MEN2).

31. Adrenal gland

32. Case 6 • 51 yr old man presents to GP for review of hypertension. He is on three agents for BP. • Has been feeling tired, weak, and been having nocturia. • BP at review: 160/110mmHg • Bloods: mild hypokalaemia • Impression? • What investigations are next?

33. Conn’s syndrome • Resistant BP + hypokalaemia • Increased aldosterone loss of K and retention of Na in distal conv tubule – retention. • Polyuria and nocturia can occur if hypokalaemic  makes kidney more resistant to ADH (which increases at night) • Ix: Serum aldoseterone, renin, and ratio.

34. Case 6 • Management • Spironolactone – (will help electrolytes and BP) • Potassium supplements may be needed in some • Surgery

35. Quick fire quiz

36. The foetal structure that gives rise to the anterior pituitary is called: • Rathke's Pouch

37. Which of the following is NOT secreted by the anterior pituitary? • (a) Growth hormone (GH). • (b) Adenocorticotrophic hormone (ACTH). • (c) Follicle Stimulating Hormone (FSH). • (d) Oxytocin.

38. Which of the following is NOT secreted by the anterior pituitary? • (a) Growth hormone (GH). • (b) Adenocorticotrophic hormone (ACTH). • (c) Follicle Stimulating Hormone (FSH). • (d) Oxytocin.

39. The cells of the adrenal cortex, from outermost to innermost, are: (a) Zonafasciculata, zonaglomerulosa, zonareticularis. • (b) Zonaglomerulosa, zonafasciculata, zonareticularis. • (c) Zonareticularis, zonafasciculata, zonaglomerulosa. • (d) Zonafasciculata, zonareticularis, zonaglomerulosa.

40. The cells of the adrenal cortex, from outermost to innermost, are: (a) Zonafasciculata, zonaglomerulosa, zonareticularis. • (b) Zonaglomerulosa, zonafasciculata, zonareticularis. • (c) Zonareticularis, zonafasciculata, zonaglomerulosa. • (d) Zonafasciculata, zonareticularis, zonaglomerulosa.

41. Which embryological arches do the parathyroids come from? • Superior: from IVthbranchial arch • Inferior: from IIIrdbranchial arch

42. What is the difference between Cushing’s Syndrome and Cushing’s Disease? • Cushing’s syndrome = too much cortisol, either exogenous or from adrenals • Cushing’s disease = pituitary adenoma is the cause – inc ACTH.

43. How do you tell the difference clinically (investigations)? • Low dose dexamethasone test • 24 hour urinary free cortisol • Plasma ACTH • High dose dexamethasone suppression test and urinary cortisol

44. Thank you