ENDOCRINE CASE STUDIES
Dr SUNIL ZACHARIAH
Consultant Endocrinologist
Spire Gatwick Park and ESH
CASE-1
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23 year old lady
3 months post delivery
Presents with palpitations and loose stools
FT4=32.6 pmol/L
TSH<0.01 mU/L
POSTPARTUM THYROIDITIS
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Incidence varies from 5-11%
More common in women with a family history
of hypothyroidism and positive TPO antibodies
CLINICAL FEATURES
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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
Pathogenesis
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Destructive autoimmune thyroiditis causing first
release of thyroxine and then hypothyroidism as
the thyroid reserve is depleted
FNAC shows lymphocytic thyroiditis
Management
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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
Case Study-2
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60 year old Type 2 Diabetes
Last HbA1c=8%(64 mmol/mol)
Presents with erectile dysfunction
Not much benefit from Viagra
Testosterone level 8 nmol/L
Hypogonadism in Type 2 Diabetes
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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 <12 nmol/L, then a 6 month
trial of testosterone is warranted
Case Study 3
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27 year old female
Follicular Cancer of Thyroid
Post surgery, post radioiodine ablation
On Thyroxine replacement (175 mcg)
FT4 19.8
TSH 0.05
Follow up of thyroid Cancer
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Original diagnosis and treatment
If total thyroidectomy and ablative radioiodine,
thyroglobulins usually undetectable if TSH
unrecordable
Maintain TSH<0.05
Case 4
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50 year old man
Ventricular tachycardia with poor LV function
Controlled on Amiodarone
FT4 50
FT3 7
TSH<0.01
Amiodarone and Thyroid
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Inhibits thyroidal iodide uptake
Inhibits conversion of T4 to T3 intracellularly
Inhibits T4 entry into cells
Direct T3 antagonism at level of cardiac tissue
Amiodarone induced hyperthyroidism
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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)
CASE 5
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32 year old female
BMI=25
Detected to have blood pressure of 210/100
mm Hg
History of palpitations, abdominal discomfort
Investigated for secondary causes of
hypertension
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
L.L.
CT Scan 1998
L.L. MIGB Scan 1998
Management of
Phaeochromocytoma
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Commenced on alpha and beta blockade
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Referred for surgery
DEFINITION
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Phaeochromocytomas are adrenomedullary
catecholamine secreting tumours
Paragangliomas are tumours arising from extraadrenal medullary neural crest derivatives, e.g.
sympathetic or carotid body, aorticopulmonary,
intravagal or parasympathetic
INCIDENCE
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Rare tumours
Accounting for <0.1% of causes of
hypertension
Can be fatal if undiagnosed
EPIDEMIOLOGY
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Equal sex distribution
Most commonly in 3rd and 4th decades
Majority(90%) are sporadic, 10% are inherited
PATHOPHYSIOLOGY
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Sporadic tumours are usually unilateral and <10
cm diameter
10-20% are malignant
Paragangliomas are more likely to be malignant
CLINICAL FEATURES
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Sustained or episodic hypertension
Sweating and heat intolerance(80%)
Headache(65%)
Palpitations(65%)
Abdominal pain
Constipation
COMPLICATIONS
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CVS: LVF, dilated cardiomyopathy
Resp: Pulmonary oedema
Neuro: Cerebrovascular, hypertensive
encephalopathy
Who should be screened?
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Family history of MEN, VHL,
Neurofibromatosis
Paroxysmal symptoms
Young hypertensive
Patient developing HT crisis during GA
Unexplained heart failure
INVESTIGATIONS
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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
LOCALIZATION
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MRI or CT scan
MIBG scan: Meta-iodobenzylguanidine is a
chromaffin-seeking analogue. Positive in 6080%.
MANAGEMENT
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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
Case Study 6
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49 year old
HGV Driver
Diagnosed type 2 diabetes 8 years ago
Diet controlled for 1 year
Check’s Blood Glucose once a day (8-13)
On tablets since then
Yearly retinal screening
MEDICATIONS
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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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Hba1c=9.2%
Creatinine=90, GFR=76
?Next Step
The incretin effect is reduced in patients
with type 2 diabetes
Intravenous Glucose
Oral Glucose
Patients with type 2 diabetes
80
80
60
60
Insulin (mU/L)
Insulin (mU/L)
Control subjects
40
* * *
*
*
*
*
20
40
*
* *
20
0
0
0
30
60 90 120 150 180
Time (min)
*P ≤.05 compared with respective value after oral load.
Nauck MA, et al. Diabetologia 1986;29:46–52.
0
30
60 90 120 150 180
Time (min)
Incretins and glycaemic control
Ingestion
of food
Glucose dependent
 Insulin
from beta cells
(GLP-1 and GIP)
GI tract
Release of
incretin gut
hormones
Pancreas
Insulin
increases
peripheral
glucose
uptake
Beta cells
Alpha cells
Blood
glucose control
Active
GLP-1 and GIP
DPP-4
enzyme
rapidly
degrades
incretins
 Glucagon
from alpha cells
(GLP-1)
Glucose dependent
Increased insulin
and decreased
glucagon
reduce
hepatic
glucose output
Adapted from 7. Drucker DJ. Cell Metab. 2006;3:153–165. 8. Miller S, St Onge EL. Ann Pharmacother 2006;40:1336-1343.
CASE STUDY-7
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88 year old lady
Diarrhoea
Abdominal pain
Weight loss
PAST MEDICAL HISTORY
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Extensive Investigations for Chronic
Diarrhoea(5 years)
Diverticular disease
Hypothyroidism
Hypertension
Ischemic Heart Disease
Hysterectomy
EXAMINATION
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Mildly dehydrated
Hypotensive (94/60 mm Hg)
Abdomen: Tenderness in Epigastrium and RUQ
CVS: Soft Systolic murmur
INVESTIGATIONS
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Hb:
WBC:
MCV:
Platelets:
Sodium:
Potassium:
Urea:
Creatinine:
CRP:
12.9
14.5
90
461
134
3.6
12.6
90
138
Bilirubin:
ALT:
Alk PO4:
Albumin:
GammaGT:
TSH:
Ft4:
T3:
Calcium:
5
61
417
42
533
3.3
12
3.2
2.4
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Urine analysis: NAD
Stool Culture, toxins and microscopy: Negative
IMAGING
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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
PATIENT PROGRESS
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Discussion with patient and family
Options discussed
Patient not keen on further invasive tests
Agreed for CT scan
CT Scan
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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
TUMOUR MARKERS
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CEA: 4.9 (0-15)
CA-125: 55 (0-35)
CA 19-9: 64 (0-27)
PROGRESS
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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 (Normal<31)
Diagnosis of Carcinoid syndrome made
Referral to Oncology and Endocrine team made
TREATMENT
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Octreotide injections started
Discharged with District Nurse input and
Oncology follow up
EPIDEMIOLOGY
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Annual incidence: 1/100000 population
Mean age: 50-60 years
Males=Females
Increased risk of developing other carcinoma’s
PATHOLOGY
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Arise from neuroendocrine cells
Characterized histologically by reaction to silver
stains and neuroendocrine markers (enolase,
chromoganin)
SITE OF OCCURENCE
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Small Intestine:
Appendix:
Rectum:
Lungs:
Rest of GIT:
Liver:
39%
26%
15%
10%
10%
2%
CLINICAL PRESENTATION
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Diarrhoea:
Flushing:
Int Obstruction:
Heart disease:
Wheezing:
Carcinoid crisis
Precipitating factors
84%
75%
44%
33%
15%
BIOCHEMICAL INVESTIGATIONS
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Urinary 5-HIAA: Sensitivity (70%), specificity
(100%)
Most sensitive marker is plasma Chromogranin
A (100%) but specificity is lower
TUMOUR LOCALIZATION
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Imaging with CT/MRI
Upper and Lower endoscope
Octreotide scan (85%): Positive scan indicates
good response to treatment with octreotide
TREATMENT
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Depends on size, location, symptom and growth
Surgery: Removal or debulking
Somatostatin analogues
Hepatic embolization
Chemotherapy/Radiotherapy
Alfa-Interferon
PROGNOSIS
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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%
CASE 8
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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)
Examination
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Height 190 cms, weight 86 kg
Large hands and feet
Prominent ridges on forehead
B/L gynaecomastia
Visual fields: Normal
Oral GTT
Time
0
20
30
60
90
120
Glucose
4.5
4.8
7.0
4.8
5.5
GH
109
665
367
196
121
Acromegaly
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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
Clinical features
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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
Diagnosis
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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
Treatment
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Transphenoidal surgery is the first line of treatment
Medical therapy