(A BIT OF) ENDOCRINE

Dr Alex Smith 12th March 2013

OVERVIEW What this will cover Cases:

Thyroid diseasePituitary diseaseAdrenal disease

A few quiz questions (if time allows) Eponymous syndromes game (woo)

What I won’t coverDiabetes and DM emergencies

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.

NECK LUMPS How do you assess?

Differential Diagnosis?

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.

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

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

NECK LUMPS Congenital

Branchial cyst Cystic hygroma Parotid tumour

Carotid body tumour Endemic Thyroid:

Thyroiditis Hashimoto’s disease Physiological Multinodular goitre

Single thyroid lumpCystAdenomaMalignancy (papillary,

follicular, medullary, anaplastic, lymphoma)

Smooth toxic goitreGraves’ diseaseDiscrete nodule in

multinodular goitreGoitrogens

THYROID CAPapillary 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).

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.

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?

CASE 2 - THIRST Urinalysis NAD BM 6.2

Baseline bloods reveal: Adj Calcium 2.8

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.

EFFECTS OF PTH

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.

CASE 3 O/e: Temperature 36.8°C RR 15 HR 85,

BP 125/65 mmHg

Neuro:PapilloedemaBitemporal hemianopia.

Impression?

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

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

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)

CASE 3: TREATMENTWhat treatment should be started?

Dopamine agonist therapy (bromocriptine, cabergoline, or quinagolide) ...(dopamine inhibits prolactin release)

Complications: nausea and vomiting, headache and mood alteration, hypotension.

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

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

CASE 4 - INVESTIGATIONS Hb 13.5 Na 127 K 5.0 Cr 120 Urea 7

Random cortisol - 250nmol/L

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)

THE ADRENALS

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) and fludrocortisone (synthetic aldosterone). Increased in times of physical stress (e.g. Infection, surgery) to avoid adrenal crisis.

Crisis: hypotension, abdominal pain, circulatory collapse

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.

CASE 5 CONTINUED O/e BP 100/80 mmHg -no postural drop pulse 86 regular. No associated lymphadenopathy Other examinations unremarkable.

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

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)

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).

ADRENAL GLAND

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: 160/110mmHgBloods: mild hypokalaemia

Impression?

What investigations are next?

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.

CASE 6 Management

Spironolactone – (will help electrolytes and BP)

Potassium supplements may be needed in some

Surgery

QUICK FIRE QUIZ

The foetal structure that gives rise to the anterior pituitary is called:

Rathke's Pouch

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.

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.

The cells of the adrenal cortex, from outermost to innermost, are:

(a) Zona fasciculata, zona glomerulosa, zona reticularis.

(b) Zona glomerulosa, zona fasciculata, zona reticularis.

(c) Zona reticularis, zona fasciculata, zona glomerulosa.

(d) Zona fasciculata, zona reticularis, zona glomerulosa.

The cells of the adrenal cortex, from outermost to innermost, are:

(a) Zona fasciculata, zona glomerulosa, zona reticularis.

(b) Zona glomerulosa, zona fasciculata, zona reticularis.

(c) Zona reticularis, zona fasciculata, zona glomerulosa.

(d) Zona fasciculata, zona reticularis, zona glomerulosa.

Which embryological arches do the parathyroids come from?

Superior: from IVth branchial arch Inferior: from IIIrd branchial arch

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.

How do you tell the difference clinically (investigations)?Low dose dexamethasone test24 hour urinary free cortisol Plasma ACTHHigh dose dexamethasone suppression test

and urinary cortisolACTH Cortisol Site

Low Not suppressed

Primary (adrenal) Cushing’s

N/High Not suppressed

Ectopic ACTH

High Suppressed by high doses

Cushing’s disease (pituitary)

THANK YOU