Objectives•Revise the pathways involved in

Adrenal Function•Define the clinical features

associated with common Adrenal Pathologies

•Interpret the investigations used in Adrenocortical abnormalities

•Outline the management of an Addisonian Crisis

Hypothalamus

CRF

Ant. Pituitary

ACTH

Adrenal Cortex

Cortisol

35 year old female.........

•feels like she has put on weight particularly on chest, stomach & face

•noticed bruising and “stretch marks”

•feels down and has no energy•periods have been quite irregular

On examination...

Investigations (bedside)

•BP-145/90 mmHg•BM-11.1 mmol/L

Investigating suspected Cushing’s

syndrome......•Plasma cortisol (raised)•Overnight dexamethasone

suppression test•Localisation tests.

Dexamethasone suppression test

•dexamethasone 1mg po at midnight

•serum cortisol at 8am•should reduce ACTH and cortisol

secretion to <50nmol/L

Localisation tests

•Plasma ACTH•If detectable.....High dose

dexamethasone suppression test.

Plasma Levels Cortisol ACTHNormal high at 8am,

low at midnightNormal (i.e. not

raised)Steroid Therapy variable Normal/

UndetectableCushing’s

syndrome(pituitary origin)

High High

Cushing’s syndrome

(adrenal origin)High Undetectable

Cushing’s syndrome

(ectopic ACTH secretion)

High Very High

Thin

Tanned

Tired

Tearful

Tummy upset

Investigations

•Postural hyotension•U&E’s-low sodium, high potassium•Low glucose

Short synacthen test

•An injection of Synacthen (250 micrograms i.m.) should cause a normal rise of cortisol in 30 minutes (>550nmol/L)

Treatment

•Steroid replacement: 15-25mg hydrocortisone daily

•Mineralocorticoid replacement: fludrocortisone daily (50-200 micrograms)

•Advice•Do not abruptly stop steroids•Give steroid card-show to

doctor/dentist etc.•Double steroids in febrile illness,

injury, stress•Add 5-10mg hydrocortisone to daily

intake before strenuous exercise

Patient collapsed in A&E.....

•D •R•A•B•C•D•E

Questions?

Summary• Describe the clinical features of the two main

Adrenal abnormalities• Know that the dexamethasone suppression

test is used in Cushing’s syndrome.• Localise the lesion responsible for excess

cortisol production based on plasma cortisol and ACTH levels

• Know that the short synacthen test is used in Addison’s disease

• Outline the management of an Addisonian Crisis.

Thyroid and parathyroid

By Laura Bond

Objectives•Understand what the thyroid and

parathyroid do and how•Get to grips with calcium homeostasis•Learn the features of thyroid and

parathyroid disease•Understand how these diseases are

treated

Hypothalamic-pituitary-thyroid

axis

Thyroid

Thyroid peroxidase

Thyroid disease

•Hyper or hypo•Primary or secondary•Many different causes

Hyperthyroidism - causes

•Autoimmune = Graves disease

•Infective = De Quervain’s thyroiditis

•Neoplastic = toxic adenoma

•Iatrogenic = drugs such as amiodarone or lithium. Also from over treating hypothyroidism

Hyperthyroidism - symptoms

• Increased metabolismweight loss and increased appetite

• Heat intolerance• Sweating• Diarrhoea• Tremor• Irritability/restlessness• Psychosis• Itch• Oligomenorrhoea

Hyperthyroidism - signs

•Increased pulse rate•atrial fibrillation•palmar erythema•hair thinning•lid retraction•goitre, nodules or

bruites

Graves disease

1. Eye signs – exomphalos, ophthalmoplegia, lid lag and lid retraction2. Pretibial myxoedema3. Thyroid acropachy

Diagnosis• TSH, free T4 and T3

• Thyroid autoantibodies – antithyroid peroxidase and antithyroglobulin antibodies.

• TSH receptor antibodies (Graves)

• US

• Isotope scan

Thyroid function tests

Test Cause

TSH, T4 Hypothyroidism

TSH, normal T4 Treated/subclinical hypothyroidism

TSH, T4 TSH tumour or hormone resistance

TSH, T4 Hyperthyroidism

TSH, normal T4 Subclinical hyperthyroidism

TSH, T4 Sick euthyroidism

Hyperthyroidism - treatment

•Medical•Beta blockers•Carbimazole•Propylthiouracil•Thyroid ablation with radioactive iodine

•Surgery•Subtotal thyroidectomy

Hypothyroidism - causes

•Autoimmune •Hashimoto’s thyroiditis •primary mxoedema (or primary

atrophic hypothyroidism)•Dietary – iodine deficiency•Iatrogenic•Congenital

Hypothyroidism - symptoms

• Tiredness• Lethargy• Depression• Cold intolerance• Weight gain• Constipation• Menorrhagia• Hoarse voice

- Dementia

Hypothyroidism - signs

•Bradycardia•Dry skin and hair•Ataxia•Slow reflexes•Peripheral neuropathy•goitre

Hypothyroidism - treatment

•levothyroxine

Any Questions?

The parathyroid gland

Hyperparathyroidism - symptoms

•bones = pain, fractures, osteopaenia and lytic lesions from bone reabsorption

•stones = kidney stones•moans = feeling crap due to depression,

tiredness, weakness•groans = abdo pain and acute abdomen

(pancreatitis, duodenal ulcers, constipation)

Hyperparathyroidism   PTH Calcium Cause

Primary solitary adenoma, hyperplasia, carcinoma

Secondary normal response to a low

Tertiary in response to long standing secondary hyperparathyroidism glands become hyperplasic

Malignant parathyroid related protein (PTrP) released by squamous cell carcinoma of lung which mimics PTH. PTrP not detected by PTH assay

Hyperparathyroidism - tests

•calcium and PTH

•ALP would be increased because of bone activity

•DEXA scan shows osteoporosis

•24 hour urinary calcium

Hyperparathyroidism - treatment

•Mild – fluids, avoid drugs, diet, review

•Severe - surgery

Hypoparathyroidism – signs and symptoms

•Tetany•Depression•Carpo-pedal spasms•Trousseau’s sign•Chvostek’s sign•ECG changes – Increased Q-T interval

Hypoparathyroidism

  PTH Calcium Cause

Primary Gland failure – autoimmune eg DiGeorge syndrome

Secondary Radiation or surgery or hypomagnesia

Pseudo Failure of target cell response to PTH. Genetic.

pseudopseudo - - Similar to pseudo but normal biochemistry

Reference rangesThyroid stimulating hormone (TSH) = 0.5-5.5 mu/l

Free thyroxine (T4) = 9-22 pmol/l

Total thyroxine (T4) = 70-140 nmol/l

3. A 36-year-old woman presents with feeling tired and cold all the time. On examination a firm, non-tender goitre is noted. Blood tests reveal the following:

TSH - 34.2 mU/lFree T4 - 5.4 pmol/l

What is the most likely diagnosis?A. Primary atrophic hypothyroidismB. Pituitary failureC. De Quervain's thyroiditisD. Iodine deficiencyE. Hashimoto's thyroiditis

A 34-year-old woman who takes hydrocortisone and fludrocortisone replacement therapy for Addison's disease presents for review. She has a three-day history of a productive cough associated with feeling hot. On examination the chest is clear, her pulse is 84 / min and temperature is 37.7ºC. You elect to prescribe an antibiotic given her medical history. What is the most appropriate advice with regard to her adrenal replacement therapy:

a)Keep the same hydrocortisone and fludrocortisone dose

b)Double both the hydrocortisone and fludrocortisone dose

c)Double the hydrocortisone dose, keep the same fludrocortisone dose

d)Convert her to prednisolone for the duration of the illness

e)Stop the hydrocortisone and fludrocortisone until the patient recovers

2. A 33-year-old female is referred by her GP with thyrotoxicosis. Following a discussion of management options she elects to have radioiodine therapy. Which one of the following is the most likely adverse effect?

A. HypothyroidismB. Thyroid malignancy C. AgranulocytosisD. OesophagitisE. Precipitation of thyroid eye disease

A 45-year-old woman is investigated for weight gain. She had had been unwell for around four months and described a combination of symptoms including depression, facial male-pattern hair growth and reduced libido. During the work-up she was found to be hypertensive with a blood pressure of 170/100 mmHg. Which one of the following tests is most likely to be diagnostic?

a)Renin:aldosterone levels

b)High-dose dexamethasone suppression test

c)Pelvic ultrasound

d)Overnight dexamethasone suppression test

e)24 hr urinary free cortisol

A 23-year-old woman presents with sweating and tremor. Her thyroid function tests are as follows: 

TSH - <0.05 mU/lFree T4 - 25 pmol/l

What is the most common cause of this presentation?A. Hashimoto's thyroiditisB. Graves' disease C. Toxic nodular goitreD. De Quervain's thyroiditisE. Toxic adenoma

4. A 43-year-old woman presents for follow-up in clinic. She was diagnosed with Hashimoto's thyroiditis four months ago and is currently being treated with levothyroxine 75 mcg od. What is the single most important blood test to assess her response to treatment?

A. ESRB. TSHC. Free T4D. Total T4E. Free T3

Which one of the following is the cause of Cushing's disease?

a)Ectopic ACTH production

b)Adrenal adenoma

c)Micronodular adrenal dysplasia

d)Adrenal carcinoma

e)Pituitary tumour

5. A 40-year-old woman complains of feeling tired all the time and putting on weight. On examination a diffuse, non-tender goitre is noted. Blood tests are ordered:TSH - 15.1 mU/lFree T4 - 7.1 pmol/lESR - 14 mm/hrAnti-TSH receptor stimulating antibodies - NegativeAnti-thyroid peroxidase antibodies - Positive

What is the most likely diagnosis?A. Pituitary failureB. Primary atrophic hypothyroidismC. De Quervain's thyroiditisD. Hashimoto's thyroiditisE. Grave's disease

A 30 year old hypertensive man presents with the following blood results:

Na 147mmol/LK 2.8 mmol/LUr 4.0 mmol/LCr 50 micromol/LGlucose 4 mmol/L

What is the diagnosis?

a) Coarctation of the aorta

b) Conn’s syndrome

c) Cushing’s disease/syndrome

d) Polycystic kidney disease

e) Primary (essential) hypertension

6. A 52-year-old woman who was diagnosed as having primary atrophic hypothyroidism 12 months ago is reviewed following recent thyroid function tests (TFTs): TSH - 12.5 mU/lFree T4 - 14 pmol/l She is currently taking 75mcg of levothyroxine once a day. How should these results be interpreted? A. Poor compliance with medicationB. Taking extra thyroxineC. Evidence of recent systemic steroid therapyD. Keep on same dose E. T4 to T3 conversion disorder

A 30-year-old woman presents to the endocrinology clinic with bruising, striae, acne and hirsutism. On examination, the patient appears lethargic and depressed, with centripetal obesity and demonstrable proximal myopathy. Blood pressure is 165/106 mmHg and blood tests reveal Na+ 136 mmol/l, K+ 2.8 mmol/l and random glucose 8.2 mmol/l. A low-dose dexamethasone test and 24-hour urinary cortisol test are ordered.

What is the most common cause of Cushing’s syndrome?

a) ectopic ACTH secretion

b) primary adrenal disorder

c) iatrogenic

d) pituitary dependent

e) pseudo-cushing’s syndrome