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Sachi Parikh scp21@ic.ac.uk Slides adapted from lecture delivered in 2023 Thyroid & Misc Endo A MedED LECTURESESSION STRUCTURE • Hyper/hypothyroidism including myxoedema coma • Understand what is meant by thyroid eye disease • Recall the symptoms and investigations for the following conditions: i. Thyroid Cancer ii. MEN Syndrome iii. Carcinoid Syndrome iv. Hypogonadism • Remember the symptoms, investigations, and management of acromegaly SBA 1 A • What antibody is most associated with Grave’s disease? a) Anti-TPO antibodies b) Anti-nuclear antibodies c) Anti-TSH receptor antibodies d) Anti-CCP antibodies e) Anti-AChR antibodies Hyperthyroidism Symptoms • Tremor Investigations • Anxiety • Palpitations T4/T3 act to • T4/TSH levels • Heat intolerance ↑metabolic rate - • Diarrhoea • Radioactive iodine uptake test • Oligomenorrhoea + TSH Anti-TSH receptor antibodies T4 ↑ Causes: + - ▪ Grave’s Disease TSH ↓ ▪ Toxic multinodular goitre ▪ Thyroiditis ▪ Drugs ( i.e. amiodaron) Management: • Propanolol • Carbimazole (TPO inhibitor) Side effects:Agranulocytosis • Radioiodine (i.e. no neutrophils)Different types of hyper/hypothyroidism Hypothyroidism+ Myxoedema coma Symptoms Myxoedema coma • Lethargy • Cold intolerance • Weight gain • Constipation • Menorrhagia • ↓Deep tendon reflexes Causes: ▪ Hashimoto’s thyroiditis ▪ Subacute (de Quervain’s) thyroiditis ▪ Drugs (i.e. amiodarone, lithium) ▪ Iodine deficiency Investigations: Management: T4 ↓ •Oxygen •Rewarming TSH ↑ Management: •Rehydration/fluids - correct electrolyte • Levothyroxine disturbance and hypoglycaemia •IV T4/T3 (liothyronine) •IV hydrocortisone (assume adrenal insufficiency until excluded)Thyroid Eye Disease Bilateral Exophthalmos Features: • Diplopia + • Conjunctival oedema (chemosis) + • Ophthalmalgia • Exposure keratopathy + • Optic Neuropathy (e.g. blurred vision) + TSH Seen in 25-50% of Grave’s Disease patients receptor Anti-TSH receptor antibodies Lid lag (and retraction) https://collections.lib.utah. edu/ark:/87278/s6sn36kf SBA 1 A • What antibody is most associated with Grave’s disease? a) Anti-TPO antibodies Hashimoto’s thyroiditis (hypothyroidism) b) Anti-nuclear antibodies SLE (anti-dsDNA antibodies) c) Anti-TSH receptor antibodies EXOMPHTHALMOS d) Anti-CCP antibodies Rheumatoid arthritis + TSH e) Anti-AChR antibodies Myasthenia graviseceptorAnantibodieseptor SBA 2 Q • A 38 year-old female presents to her GP with a 4-month history of unintentional weight loss and difficulty swallowing. Friends have said her voice sounds different. On examination, a firm non-tender nodule is palpated in the front of her neck. What is the most likely diagnosis? a) Anaplastic carcinoma b) Oesophageal carcinoma c) Follicular carcinoma d) Hürthle cell carcinoma e) Papillary carcinoma Thyroid Cancer Does anyone know Trachea what this is showing? Features: • Non-functional, painless, rapidly growing • Solitary, irregular (nodular) shape • Palpable nodule, hard and fixed • Hoarse voice • Dysphagia • Haemoptysis • Airway obstruction • Cervical lymphadenopathy Right recurrent Left recurrent Psammoma Body laryngeal nerve laryngeal nerve Papillary carcinoma (70%) 20-40 year-old female with childhood radiation exposure-excellent prognosis 40-60-year-old female with low dietary iodine intake Follicular carcinoma (20%) n Features- hurthle cells, commonly metastasises to cervical lymph nodes o m Medullary carcinoma (5%) Associated with MEN 2A & MEN 2B, high calcitonin+hypocalcemia o C Anaplastic carcinoma (1%)- extremely poor prognosis, in the elderly Ix: FNAB w/ USS, CT/PET, Thyroid scan ~TFTs may be useful to exclude benign Lymphoma (rare) (functional) nodules SBA 2 A • A 38-year-old female presents to her GP with a 4-month history of unintentional weight loss and difficulty swallowing. Friends have said her voice sounds different. On examination, a firm non-tender nodule is palpated in the front of her neck. What is the most likely diagnosis? a) Anaplastic carcinoma b) Oesophageal carcinoma c) Follicular carcinoma d) Hürthle cell carcinoma e) Papillary carcinoma Q SBA 3 • A 27-year-old tall, thin man attends A&E with severe right-sided loin pain that “comes and goes”. He also complains of new- onset ‘heart burn’ and abdominal pain. He explains that his father recently had surgery on his neck. What is the most likely diagnosis? 2+ 3.1 mmol/L a) MEN 2B Syndrome Ca (2.2-2.6) PTH 1.7 pmol/L b) MEN 1 Syndrome (1.6-6.9) c) Primary hyperparathyroidism d) Carcinoid Syndrome e) MEN 2A Syndrome What are the MEN Syndrome symptoms of hypercalcaemia? 3 P’s 2 P’s 1 P’s MEN 1 MEN 2A MEN 2B 2+ • Parathyroid HyperPTH + ↑↑Ca Medullary thyroid cancer + • Pancreatic Peptic ulcers • Pituitary ↓Libido, Mass effect • Parathyroid • Phaeochromocytoma • Others (e.g. carcinoid*, adrenal, • Phaeochromocytoma • Neuromas thyroid) • Marfanoid habitus* “Stones, groans, bones, and moans” NB: Both MEN 2A& 2B present later in • MEN1 mutation = high penetrance life than MEN 1 (Develop syndrome in early life) • MEN 2A > MEN 2B Ix: CT/MRI (whole body), genetics MEN 2A & 2B ~Zollinger-Ellison syndrome = non- Ix: Genetic testing (RET oncogene), calcitonin, urine catecholamines, CT/MRI MEN1 gastrinomasMEN Syndrome Summary 3 P’s 2 P’s 1 P’s SBA 3 A • A 27-year-old tall, thin man attends A&E with severe right-sided loin pain that “comes and goes”. He also complains of new- onset ‘heart burn’ and abdominal pain. He explains that his father recently had surgery on his neck. What is the most likely diagnosis? 3.1 mmol/L a) MEN 2B Syndrome Ca2+ (2.2-2.6) 1.7 pmol/L b) MEN 1 Syndrome PTH (1.6-6.9) c) Primary hyperparathyroidism What does this calcium study show? Primary d) Carcinoid Syndrome hyperparathyroidism “PTH is inappropriately normal” e) MEN 2A Syndrome SBA 4 Q • What is the most common presenting feature of carcinoid syndrome? a) Itching b) Shortness of breath c) Diarrhoea d) Flushing e) Abdominal pain Carcinoid Syndrome Increased circulatingFeatures: Uncontrolled *to liver*se hormone • Flushing cell division • Diarrhoea • SOB ↑ Serotonin ↑ Bradykinin • Pulmonary stenosis Neuroendocrine cell Carcinoid Tumour ↑ Histamine • Abdo pain • Itching Other facts: • Tumours are slow-growing Urine • Adults >> Children Serotonin 5-Hydroxyindole acetic acid • MEN 1 gene mutation (5-HIAA) Investigations: Somatostatin - Serotonin • Urinary 5-HIAA (screening) • CT scan Octreotide • Octreotide scan Neuroendocrine cell • Etc. SBA 4 A • What is the most common presenting feature of carcinoid syndrome? a) Itching b) Shortness of breath c) Diarrhoea d) Flushing e) Abdominal pain SBA 5 Q • A 26-year-old woman sees her GP as she has been struggling to conceive for over 14 months whilst having regular sexual intercourse. Her PMH includes acne and irregular periods. On examination, she is overweight and has abnormal hair growth on the sides of her cheeks. What is the most likely diagnosis? a) Turner’s Syndrome b) PCOS c) Primary ovarian failure d) Hypothyroidism e) Hypothalamic amenorrhoea What karyotype is Hypogonadism (Female) Turner’s Syndrome Hypothalamus characterised by? GnRH Physiological • Pregnancy + Primary Anterior pituitary • Gonadal dysgenesis (e.g. Turner’s Gonadootrophs Syndrome) • Gonadal damage Oestrogen & Testosterone LH/FSH Progesterone • Primary ovarian failure • PCOS + Secondary • Kallmann Syndrome • Pituitary/hypothalamic tumour • Hyperprolactinaemia • Functional (i.e. hypothalamic amenorrho)a • Low BMI, excess exercise, stress What symptom typically • Contraceptive pill use presents with hypogonadism in Kallmann Syndrome? Hypogonadism (Male) Hypothalamus What karyotype is Klinefelter’s GnRH Syndrome characterised by? Primary • Gonadal dysgenesis (e.g. Klinefelter’s Anterior pituitary Syndrome, cryptorchidism) Gonadootrophs • Gonadal damage • Post-orchitis (i.e. Mumps) Testosterone LH/FSH Oestrogen & Progesterone + Secondary • Kallmann Syndrome • Pituitary/hypothalamic tumour • Hyperprolactinaemia Hypogonadism Features: • Delayed puberty • Infertility • ↓ Libido • Amenorrhoea • Night sweats/hot flushes Female-specific • Erectile dysfunction Male-specific • Symptoms of cause Investigations: • Pregnancy test • LH/FSH • Prolactin • Testosterone/Oestradiol Blood tests • TFTs • Karyotyping • MRI HPS Axis Hypothalamus GHRH Somatostatin + + ↑ Cell division ↓ Apoptosis + ↑ Cellular metabolism Anterior pituitary Somatotrophs IGF-1 Insulin-like growth factor 1 GH ↑ Blood glucose ↑ Insulin resistance ↑ Muscle growth ↑ Bone thickness SBA 5 Q • A 26-year-old woman sees her GP as she has been struggling to conceive for over 14 months whilst having regular sexual intercourse. Her PMH includes acne and irregular periods. On examination, she is overweight and has abnormal hair growth on the sides of her cheeks. What is the most likely diagnosis? a) Turner’s Syndrome b) PCOS c) Primary ovarian failure d) Hypothyroidism e) Hypothalamic amenorrhoea SBA 6 Q • What would an OGTT show in a patient with severe acromegaly? a) Increased glucose b) Decreased GH c) Increased GH d) Increased insulin e) Decreased glucose Does anyone know Acromegaly a complication of acromegaly? Complications: Pituitary adenoma • Carpal tunnel syndrome (of somatotrophs) • Hypertension What visual • Diabetes mellitus disturbance • Cardiomyopathy would be • Colorectal cancer seen? Headaches ↑↑ GH Visual disturbance Acromegaly Hyperprolactinaemia Hypopituitarism “Paradoxical rise” ↑↑ IGF-1 Features: Bitemporal hemianopia • Coarse facial features • Prognathism & large tongue Management: • Spade-like hands & large feet • Trans-sphenoidal surgery • Excessive sweating • Radiotherapy Name a Investigations: • Organomegaly • Somatostatin analogues • OGTT • Dopamine receptor agonists somatostatin • Plasma IGF-1 Gigantism → growth of long bones • GH-receptor antagonists analogue • MRI • Prolactin levels A SBA 6 • What would an OGTT show in a patient with severe acromegaly? a) Increased glucose b) Decreased GH c) Increased GH Acromegaly d) Increased insulin Control “Paradoxical rise” e) Decreased glucosein feedbacknd please fill