ENDOCRINE CASE STUDIES

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ENDOCRINE CASE STUDIES

• Dr SUNIL ZACHARIAH
• Consultant Endocrinologist
• Spire Gatwick Park and ESH

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CASE-1

• 23 year old lady
• 3 months post delivery
• Presents with palpitations and loose stools
• FT432.6 pmol/L
• TSHlt0.01 mU/L

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POSTPARTUM THYROIDITIS

• Incidence varies from 5-11
• More common in women with a family history of
  hypothyroidism and positive TPO antibodies

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CLINICAL FEATURES

• Presentation is usually 3-4 months postpartum
• Can be hypothyroidism (40), hyperthyroidism
  (40) or biphasic(20)
• Goiter is present in 50 of patients
• To distinguish from Graves disease use thyroid
  isotope scan and TSH receptor Ab

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Pathogenesis

• Destructive autoimmune thyroiditis causing first
  release of thyroxine and then hypothyroidism as
  the thyroid reserve is depleted
• FNAC shows lymphocytic thyroiditis

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Management

• Most patients recover spontaneously without
  requiring treatment
• If hyperthyroid use beta blockers rather than
  antithyroid drugs as the problem is increased
  release, not synthesis
• Hypothyroid phase is more likely to require
  treatment
• Only 3-4 remain permanently hypothyroid
• 10-25 will recur in future pregnancies

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Case Study-2

• 60 year old Type 2 Diabetes
• Last HbA1c8(64 mmol/mol)
• Presents with erectile dysfunction
• Not much benefit from Viagra
• Testosterone level 8 nmol/L

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Hypogonadism in Type 2 Diabetes

• Low testosterone levels are common in people with
  type 2 diabetes
• Effect of testosterone replacement on glycaemic
  control remains uncertain
• If androgen deficiency is suspected then do at
  least two 9 am testosterone levels. If first
  sample is low , then check LH, FSH, SHBG,
  ferritin and prolactin as well in the 2nd sample

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• If testosterone level is between 8 and 12 nmol/L
  in a symptomatic individual, then a trial of
  testosterone replacement is warranted
• If the man has tried a phosphodiesterase
  inhibitor without success and has a total
  testosterone of lt12 nmol/L, then a 6 month trial
  of testosterone is warranted

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Case Study 3

• 27 year old female
• Follicular Cancer of Thyroid
• Post surgery, post radioiodine ablation
• On Thyroxine replacement (175 mcg)
• FT4 19.8
• TSH 0.05

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Follow up of thyroid Cancer

• Original diagnosis and treatment
• If total thyroidectomy and ablative radioiodine,
  thyroglobulins usually undetectable if TSH
  unrecordable
• Maintain TSHlt0.05

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Case 4

• 50 year old man
• Ventricular tachycardia with poor LV function
• Controlled on Amiodarone
• FT4 50
• FT3 7
• TSHlt0.01

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Amiodarone and Thyroid

• Inhibits thyroidal iodide uptake
• Inhibits conversion of T4 to T3 intracellularly
• Inhibits T4 entry into cells
• Direct T3 antagonism at level of cardiac tissue

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Amiodarone induced hyperthyroidism

• 2-12
• Type 1 Iodine overload in abnormal gland, treat
  with carbimazole or lithium
• Type 2 Glandular damage, release of preformed
  hormones, treat with prednisolone 0.5-1.25 mg/kg
  for 3-6 weeks
• Management of tachyarrhythmia's beta blockers if
  not in CCF
• ?total thyroidectomy (not radioiodine)

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CASE 5

• 32 year old female
• BMI25
• Detected to have blood pressure of 210/100 mm Hg
• History of palpitations, abdominal discomfort
• Investigated for secondary causes of hypertension

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24hr Urinary collections
6/3/98 8/3/98 11/3/98
VMA (5-35) 154 225 192
Normetanephrine (0.1 1.3) 34.8 59.5 54.9
Metanephrine (0.1 1.3) 0.4 0.6 0.7
3-methoxytyranine (0.1 2.0) 4.8 5.6 6,5
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L.L. CT Scan 1998
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L.L. MIGB Scan 1998
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Management of Phaeochromocytoma

• Commenced on alpha and beta blockade
• Referred for surgery

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DEFINITION

• Phaeochromocytomas are adrenomedullary
  catecholamine secreting tumours
• Paragangliomas are tumours arising from
  extra-adrenal medullary neural crest derivatives,
  e.g. sympathetic or carotid body,
  aorticopulmonary, intravagal or parasympathetic

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INCIDENCE

• Rare tumours
• Accounting for lt0.1 of causes of hypertension
• Can be fatal if undiagnosed

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EPIDEMIOLOGY

• Equal sex distribution
• Most commonly in 3rd and 4th decades
• Majority(90) are sporadic, 10 are inherited

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PATHOPHYSIOLOGY

• Sporadic tumours are usually unilateral and lt10
  cm diameter
• 10-20 are malignant
• Paragangliomas are more likely to be malignant

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CLINICAL FEATURES

• Sustained or episodic hypertension
• Sweating and heat intolerance(80)
• Headache(65)
• Palpitations(65)
• Abdominal pain
• Constipation

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COMPLICATIONS

• CVS LVF, dilated cardiomyopathy
• Resp Pulmonary oedema
• Neuro Cerebrovascular, hypertensive
  encephalopathy

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Who should be screened?

• Family history of MEN, VHL, Neurofibromatosis
• Paroxysmal symptoms
• Young hypertensive
• Patient developing HT crisis during GA
• Unexplained heart failure

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INVESTIGATIONS

• 24 hour urine collection for catecholamines.
  Because of episodic nature at least two 24 hour
  samples
• Plasma catecholamines Limited use because of
  intermittent secretion. Useful if patient having
  a crisis
• Screening for associated conditions

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LOCALIZATION

• MRI or CT scan
• MIBG scan Meta-iodobenzylguanidine is a
  chromaffin-seeking analogue. Positive in 60-80.

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MANAGEMENT

• Alfa-blockade (Phenoxybenzamine) must be
  commenced before beta-blockade to avoid
  precipitating a hypertensive crisis due to
  unopposed alfa-adrenergic stimulation
• Surgical resection (open or laparoscopic)
• Malignancy High dose MIBG therapy, Chemotherapy,
  Octreotide therapy

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Case Study 6

• 49 year old
• HGV Driver
• Diagnosed type 2 diabetes 8 years ago
• Diet controlled for 1 year
• Checks Blood Glucose once a day (8-13)
• On tablets since then
• Yearly retinal screening

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MEDICATIONS

• Metformin 1 gm bd
• Pioglitazone 45 mg od
• Gliclazide 80 mg bd
• Lipitor 40 mg od
• Perindopril 4 mg od
• Aspirin 75 mg od

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• Hba1c9.2
• Creatinine90, GFR76
• ?Next Step

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The incretin effect is reduced in patients with
type 2 diabetes
Intravenous Glucose
Oral Glucose
Control subjects
Patients with type 2 diabetes
80
80
60
60
Insulin (mU/L)
Insulin (mU/L)
40
40
20
20
0
0
0
30
60
90
120
150
180
0
30
60
90
120
150
180
Time (min)
Time (min)
P .05 compared with respective value after oral
load. Nauck MA, et al. Diabetologia
1986294652.
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Incretins and glycaemic control
Bloodglucose control
DPP-4enzyme rapidly degrades incretins
Adapted from 7. Drucker DJ. Cell Metab.
20063153165. 8. Miller S, St Onge EL. Ann
Pharmacother 2006401336-1343.
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CASE STUDY-7

• 88 year old lady
• Diarrhoea
• Abdominal pain
• Weight loss

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PAST MEDICAL HISTORY

• Extensive Investigations for Chronic Diarrhoea(5
  years)
• Diverticular disease
• Hypothyroidism
• Hypertension
• Ischemic Heart Disease
• Hysterectomy

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EXAMINATION

• Mildly dehydrated
• Hypotensive (94/60 mm Hg)
• Abdomen Tenderness in Epigastrium and RUQ
• CVS Soft Systolic murmur

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INVESTIGATIONS

• Hb 12.9 Bilirubin
  5
• WBC 14.5 ALT
  61
• MCV 90 Alk PO4
  417
• Platelets 461 Albumin
  42
• Sodium 134 GammaGT 533
• Potassium 3.6 TSH
  3.3
• Urea 12.6 Ft4
  12
• Creatinine 90 T3
  3.2
• CRP 138 Calcium
  2.4

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• Urine analysis NAD
• Stool Culture, toxins and microscopy Negative

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IMAGING

• CXR Normal
• Ultrasound Abdomen Hepatomegaly, with multiple
  avascular, iso-echoic lesions in both lobes of
  liver representing metastasis. Primary likely to
  be ?colorectal or ?pulmonary

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PATIENT PROGRESS

• Discussion with patient and family
• Options discussed
• Patient not keen on further invasive tests
• Agreed for CT scan

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CT Scan

• No significant lymphadenopathy
• No significant lung lesions
• Liver is replaced by multiple metastasis in both
  lobes
• Normal pancreas and adrenals
• No masses in the ovary or large bowel

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TUMOUR MARKERS

• CEA 4.9 (0-15)
• CA-125 55 (0-35)
• CA 19-9 64 (0-27)

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PROGRESS

• Diarrhoea persisting
• General condition of patient, however good
• History reviewed with patient Feeling flushed
  for many months
• Could this be Carcinoid?

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• 24 hour 5 HIAA requested
• Laboratory reluctant
• Result 672 (Normallt31)
• Diagnosis of Carcinoid syndrome made
• Referral to Oncology and Endocrine team made

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TREATMENT

• Octreotide injections started
• Discharged with District Nurse input and Oncology
  follow up

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EPIDEMIOLOGY

• Annual incidence 1/100000 population
• Mean age 50-60 years
• MalesFemales
• Increased risk of developing other carcinomas

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PATHOLOGY

• Arise from neuroendocrine cells
• Characterized histologically by reaction to
  silver stains and neuroendocrine markers
  (enolase, chromoganin)

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SITE OF OCCURENCE

• Small Intestine 39
• Appendix 26
• Rectum 15
• Lungs 10
• Rest of GIT 10
• Liver 2

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CLINICAL PRESENTATION

• Diarrhoea 84
• Flushing 75
• Int Obstruction 44
• Heart disease 33
• Wheezing 15
• Carcinoid crisis
• Precipitating factors

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BIOCHEMICAL INVESTIGATIONS

• Urinary 5-HIAA Sensitivity (70), specificity
  (100)
• Most sensitive marker is plasma Chromogranin A
  (100) but specificity is lower

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TUMOUR LOCALIZATION

• Imaging with CT/MRI
• Upper and Lower endoscope
• Octreotide scan (85) Positive scan indicates
  good response to treatment with octreotide

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TREATMENT

• Depends on size, location, symptom and growth
• Surgery Removal or debulking
• Somatostatin analogues
• Hepatic embolization
• Chemotherapy/Radiotherapy
• Alfa-Interferon

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PROGNOSIS

• If detected early, results in complete and
  permanent cure
• Median survival rate improved to 12 years.
  especially after introduction of somatostatin
  analogues
• If Liver metastasis, 5 year survival is 20-40

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CASE 8

• 15 year old boy
• GP referral Concerns expressed by mother
  regarding height velocity
• Already 190 cms Mother 163 cms and Father 170
  cms
• Feet size 16

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• Had started growing at a rapid pace since the age
  of 12 (0.5 1 inch a month)
• Sweaty palms
• Pain in knees and wrists
• Pins needles in both hands

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• No headache or visual symptoms
• Normal pubertal development
• 2nd tallest in his class!!!!!!
• Enjoys sports and other activities at school, but
  is troubled by knee pain
• Developmental milestones were normal

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• Initial Ix done by GP revealed
• - Prolactin 1656 mu/L (86-324)
• - Testosterone 1.6 nmol (10-28)
• FSH, LH within normal range
• - Normal TFT

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• IGF-1 151 nmol/L (30-90)

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Examination

• Height 190 cms, weight 86 kg
• Large hands and feet
• Prominent ridges on forehead
• B/L gynaecomastia
• Visual fields Normal

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Oral GTT

• Time Glucose GH
• 0 4.5
  109
• 20 -
  -
• 30 4.8
  665
• 60 7.0
  367
• 90 4.8
  196
• 120 5.5 121

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Acromegaly

• Uncommon condition, new case incidence 3-4 per
  million, mean age of diagnosis 40-45
• More than 95 caused by pituitary adenoma, rarely
  by ectopic GH or GHRH production by malignant
  tumours
• All cause mortality rate is twice that of normal
  population is due to cardiac, cerebrovascular,
  Diabetes neoplasia (colon cancer) related

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Clinical features

• Due to soft tissue enlargement in all organ
  systems or due to presence of tumour in pituitary
  fossa
• Headache and visual field defect
• Increase in ring/shoe size, hyperhidrosis,
  coarsening of facial features, prognathism,
  macroglossia, arthritis
• Glucose intolerance or diabetes, hypertension, CV
  disease, cardiomyopathy
• Increased incidence of Ca colon

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Diagnosis

• Oral GTT Gold standard for diagnosis
• Imaging MRI should only be done after a firm
  biochemical diagnosis, because of high incidence
  of non-functioning adenomas
• IGF 1 Useful in screening and to monitor Rx

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Treatment

• Transphenoidal surgery is the first line of
  treatment
• Medical therapy