Neck and Hormones

  • 341 views
Uploaded on

 

  • Full Name Full Name Comment goes here.
    Are you sure you want to
    Your message goes here
    Be the first to comment
    Be the first to like this
No Downloads

Views

Total Views
341
On Slideshare
0
From Embeds
0
Number of Embeds
0

Actions

Shares
Downloads
7
Comments
0
Likes
0

Embeds 0

No embeds

Report content

Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
    No notes for slide
  • Prevalences UK, depending on definitions,
  • Prevalence ca 2.7% UK in females, ca 0.3% in males. Overall ca 1 : 1000 in females
  • With globalization and immigration, TPP is no longer confined to certain geographic areas and has been increasingly reported throughout the world.
  • T3 thyrotoxicosis mainly seen in XXX US scan helps to differentiate between AIT, Graves`, and toxic adenoma adenomas that produce overt hyperthyroidism generally are ≥ 3 cm
  • Increase of TSH with metoclopramide (Scanlon JCEM 1980)
  • tonic inhibitory role for DA in the control of TSH secretion
  • PTU: also fulminant hepatitis But evl smaller risk of XXX
  • PTH results came back later, hence initially thought to have multiple myeloma
  • Clinical correlates may include bone pain and tenderness, bowing of the shoulders, kyphosis and loss of height, collapse of lateral ribs and pelvis with pigeon breast and triradiate deformities, respectively
  • Moosgaard Denmark 81% vs 60% in controls Ca 20% (McDermott p 136) Subjects with primary hyperparathyroidism were 3.34 kg (95% confidence interval, 1.97-4.71; P < 0.00001) heavier than controls in 13 studies reporting body weight. In four studies reporting body mass index, subjects with primary hyperparathyroidism had an increased body mass index of 1.13 kg/m(2) (-0.29 to 2.55; P = 0.12) compared with controls.
  • Cholecalciferol tablets 1.25 mg (50000 units)
  • Eastell JCEM 2009, Holick NEJM 2007, Tucci EJE 2009
  • 1,25(OH) 2 D Calcitriol; 25(OH)D Vit D
  • Unless homozygous, in newborns CHECK pHPT Ca/Crea Cl > 0.02 CHECK
  • Grandmother had the same association, age 55 years don’t make the diagnosis without family screening
  • Addisons, ketoacidosis

Transcript

  • 1. Grand Round 06/10/2009 Martin O. Weickert and colleagues Neck & Hormones Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism
  • 2.
    • thyroid
      • thyrotoxicosis (2% of UK population)
      • hypothyroidism
      • (9.3% (w), >60 yrs up to 16%; 1.35% (m))
    • parathyroid glands
      • hyperparathyroidism
      • (prim HPT < 0.1 – 3.4%, ↑ with age;
      • sec HPT i.e. 80% in chronic haemodialysis
      • patients )
      • hypoparathyroidism
      • (most common post-surgery;
      • otherwise rare)
    Endocrine active organs in the neck Yu et al. Clin Endocrinol 2009; Franklyn ESE abstracts 2009
  • 3. An interesting case…. Steph Horne House Officer
  • 4. Demographics
    • 35 year old Caucasian Female
    • self admission to A&E
  • 5. Presenting complaint
    • upper abdominal pain
    • epigastric area: burning/sharp in nature
    • bloody diarrhoea
    • vomited 15 times, diarrhoea for 5 days
    • not able to tolerate any oral food/fluids
    • similar episode 6 months ago
    • OP endoscopy booked but DNA
  • 6. And the rest…
    • PMHX:
      • appendix removed 6 years ago
      • hyperthyroidism
      • anxiety
    • SHX:
      • smoker 4-5 per day
      • mild alcohol intake
      • on methadone treatment
  • 7. On examination: Chest clear HS I + II + 0 CNS intact Temperature: 36.3 BP: 174/112 PR: 99 RR: 24 O2 Sats: 99% OA Mews: 2 Pain score: 3 (0-3) Epigastric pain No Organomegaly BS + Unable to demonstrate guarding PR: Empty Rectum
  • 8. Impression…..
    • perforated ulcer
    • gallstones
    • GORD
    • pancreatitis
    • gastroenteritis
  • 9. The blood results…
    • electrolytes: NAD
    • WCC: 14.42, Hb: 11.8, Plts: 417
    • alk Phos: 227, ALT: 36, Amylase: 33
  • 10. TIMELINE Surgical team referral Admitted to SAU OGD and Colonoscopy Discussions re; Laparotomy A&E: Abdo pain and diarrhoea Impression: Acute abdomen AXR/CXR: NAD Gastro referral
  • 11. Then along came….
    • TSH < 0.02 mU/L (0.35 – 6 mU/L)
    • free T3 – 36.3 pmol/L (2.8 – 7.1 pmol/L)
    • free T4 – > 100 pmol/L (9 – 26 pmol/L)
    Thyrotoxicosis
  • 12. Treatment…
    • symptomatic relief : beta blockers
    • carbimazole
    • USS thyroid gland
    • thyroid autoantibodies
  • 13. The result…
    • diarrhoea resolved
    • tremor/anxiety improved
    • discharged with endocrine follow up
  • 14. Common causes of thyrotoxicosis
    • Graves` disease
    • toxic adenomas
    • toxic multinodular goitre
    • thyroiditis
    • ingestion of excessive exogenous thyroid hormone
      • iatrogenic, inadvertent, or surreptitious
  • 15. Some rarer causes
    • TSH-secreting pituitary adenoma
    • struma ovarii
      • ectopic production in ovarian teratomas
    • extremly high levels of hCG
      • choriocarcinomas, germ cell tumours
  • 16. “ Classical” symptoms of thyrotoxicosis
    • hyperactivity, irritability, altered mood
    • sleep disturbances
    • sweating, heat intolerance
    • palpitations
    • weight loss, occasionally weight gain (polyphagia)
    • oligo-/amenorrhoea, loss of libido
  • 17. unspecific in aged patients...
    • tiredness, apathy, depression
    • „ dementia“, confusion, psychosis
    • GI symptoms
    • AF, worsening of angina pectoris, or congestive heart failure
  • 18. Thyrotoxic periodic paralysis (TPP)
    • 2% in Asians, rare in Caucasians (0.15%)
    • hyperthyroidism-related hypokalaemia
    • sudden shift of K+ into cells
      • associated with exercise
      • inducible by carbohydrate + insulin challenge
    • presentation in ED with
      • acute muscle weakness
      • systolic hypertension, tachycardia, high QRS voltage, first degree AV block
    McFadzean BMJ 1967, Lin Mayo Clin Proc 2005
  • 19. Biochemical findings in thyrotoxicosis
    • low TSH
  • 20. Other states with low TSH
    • secondary hypothyroidism
      • low normal or normal TSH
      • low fT4
      • usually associated with deficiencies of other pituitary hormones
    • thyroid sick syndrome
      • ? aquired transient central hypothyroidism (Chopra JCEM 1997)
      • low TSH (but not completely suppressed)
      • low fT4 and fT3
  • 21. Biochemical findings in thyrotoxicosis
    • low or suppressed TSH
    • increased fT4 and/or fT3 in overt thyrotoxicosis
      • check for isolated fT3 thyrotoxicosis
    • normal fT4 and/or fT3 in „subclinical“ thyrotoxicosis
      • increased risk of osteoporosis; evtl symptomatic
    • frequently increased auto-Abs level in AIT
  • 22. Further changes...
    • normocytic anaemia
    • increased LFTs
    • increased bone AP
    • hypercalcaemia, hyperphosphataemia
    • low albumin
    • mild leukopenia
    • low cholesterol
  • 23. 24-hour variation of TSH adapted from McDermott: Sleep and Endocrinology 2009 Hormone Circadian Sleep-wake homeostasis Cortisol +++ + Testosterone +++ - GH + +++ PRL ++ +++
  • 24. 24-hour variation of TSH adapted from McDermott: Sleep and Endocrinology 2009; Patel Clin Sci 1972 Hormone Circadian Sleep-wake homeostasis Cortisol +++ + Testosterone +++ - GH + +++ PRL ++ +++ TSH +++ ++
  • 25. Circadian rhythm of TSH
    • ? less bioactive and differently glycosylated TSH molecules secreted during the night
    • (Persani et al JCEM 1995)
    Russell et al. JCEM 2009
  • 26. Circadian rhythm of TSH and fT3
    • circadian rhythm of fT3
    • delayed by 90 min
    • clinical relevance?
    • drug induced increase of TSH, e.g. metoclopramide (Scanlon JCEM 1980))
    Russell et al. JCEM 2009
  • 27. Interaction with SHBG
    • oral contraceptives may not be fully protective in thyrotoxicosis
      • ↑ SHBG (Ford Clin End 1992)
      • ↑ clearance of contraceptives
    • caution in fertile female patients after radioiodine therapy
  • 28. An orthopaedic outlier ! Noushad
  • 29. History
    • 59 year old lady
    • attended A&E at 01.42 am, 16/7/09
    • fell down in the toilet
    • injury to left arm
    • deformity of left arm
    No orthopaedic intervention needed! W20
  • 30. History
    • increasing confusion- 16 weeks
    • weight loss and bilateral leg pains for the same period
    • was not mobilising, just stayed in bed!
    • no medical help sought until the fall
    • fracture of right olecranon in 2006 after a trivial fall
  • 31. Further story
    • left humerus was painful and deformed
    • X-ray showed
    • referred to ortho
    • ‘ no ortho intervention needed, can go home with fracture clinic appointment’
  • 32. Further story
    • patient’s daughters mentioned the poor physical and mental state, refuses to take her home
    • 04.45- patient c/o of right thigh pain
    • X-ray ordered
  • 33. Blood investigations
    • urea 9.0, creatinine 64, Na 143, K 4.0
    • adjusted Ca 3.68, ALP 606, Alb 41
    • Hb 11.0, WCC 17.36, Neuts 15.29
    • TSH 2.71
    • CRP <3
  • 34. Further investigations
    • myeloma screen negative
    • PTH 114.2 (NR1.1-4.2), Vitamin D 11.0 (NR 10-60)
    • in the meanwhile patient was reviewed by T&O team
    • ‘pathological fractures due to likely malignancy’,
    • admitted to medical ward (20), for joint care
  • 35. Management
    • final diagnosis- primary hyperparathyroidism with pathological fractures
    • patient transferred to orthopaedic ward
    • close input from endocrine team
    • MIBI scan and USS neck- Left inferior parathyroid adenoma
  • 36. Management
    • IV N.Saline 4L/day
    • IV pamidronate
    • pain relief
    • traction for fracture femur
    • cast for fracture humerus
  • 37. Other x-rays
  • 38. Management
    • left inferior parathyroidectomy 17/8/09
    • severe hypocalcaemia expected
    • ergocalciferol (Vitamin D2) 300,000 units i.m. given after parathyroidectomy
    • sandocal 1gram TDS started
  • 39. Ca 2+ and PTH trends post op Date Calcium(2.1-2.58) PTH(1.1-4.2) ALP(30-120) 16/7/09 3.68 114.2 606 16/8/09 2.76 450 17/8/09 2.61 18/8/09 2.41 18/8/09 2.35 0.8 437 18/8/09 2.26 0.6 405 19/8/09 2.28 452 21/8/09 1.99 5.6 26/8/09 1.93 16.5 711 30/8/09 1.92 36.4 658 1/9/09 1.87 45.4 574 18/9/09 2.13 24.9 325 3/10/09 2.18 223
  • 40. Current management
    • sandocal 1gram TDS
    • alfacalcidol 1microgram/day
    • traction down
    • still an inpatient
    • not yet weight bearing
  • 41. Follow up x-rays- 30/9/09
  • 42. Hungry bone syndrome
    • excessive skeletal remineralization once skeleton released from PTH excess
    • ongoing ↑ALP, ↓Ca, ↓Ph, ↓Mg
    • hypocalcaemia in pre-existing VitD deficiency
    • may require large doses of VitD/derivates and calcium for weeks to month
  • 43. Primary hyperparathyroidism (pHPT)
    • „ stones, bones, abdominal groans …“
    • depression
    • „ stones, bones, abdominal groans, and psychic moans …“
  • 44. Modern vs classical pHPT
    • abrupt increase in annual incidence since the early 1970s
      • 0.15 (1965 – 1974) to 1.12 (1975) per 1000 persons (Wermers Ann Int Med 1997)
      • introduction of screening
    • > 85% of modern pHPT patients are asymptomatic or have unspecific symptoms
  • 45. Modern vs classical pHPT
    • kidney stones only in 15-20% of patients with „modern“ pHPT
    • reduced BMD
    • far subtler abnormalities in bone
    • often radiographics NAD
    • routine skeletal x-rays are no longer recommended (Bilezikian et al. JCEM 2002)
  • 46. Biochemical findings in pHPT
    • increased PTH
    • increased (or normal) calcium
    • low normal fasting serum phosphate
    • other associated findings may include
      • increased chloride, Cl/phosphate ratio ≥ 33, elevated urinary pH (> 6), increased alkaline phosphatase
  • 47. Band keratopathy
    • calcium-phosphate precipitation in medial and limbic margins of cornea
  • 48. Parathyroid bone disease
    • thin cortices
    • contrasting maintenance of trabecular bone
    Parisien et al. JCEM 1990 patient with pHPT control Biopsy specimens from iliac crest
  • 49. Osteitis fibrosa cystica
    • striking and generalised increase in osteoclastic bone resorption
    • osteoclastomas ( brown tumours ) with osteous expansion and lucency
    • fibrovascular marrow replacement
    • increased osteoblastic activity
  • 50. salt-and-pepper appearance of the calvarium trabecular bone resorption with loss of definition of cortices
  • 51. subperiostal bone resorption along the radial aspects of the middle phalanges distal clavicular resorption radiological disappearance of some bones
  • 52. pHPT and vitamin D deficiency
    • modern pHPT: bone disease mainly in patients with severe vitamin D deficiency
    • however
    • co-existing pHPT and vitamin D deficiency is very common! (Mossgaard Clin End 2005, Eastell JCEM 2009)
      • association with ↑ PTH, Ca, ALP, accelerated bone turnover, larger parathyroid glands/tumours, greater likelihood of abnormal bones (Tucci Eur J Endocrinol 2009)
      • calcium levels can also be normal
  • 53. Grey et al. JCEM 2005
  • 54. Grey et al. JCEM 2005 Cholecalciferol tablets 1.25 mg (50000 units) weekly for 4 weeks, thereafter 1 tablet per month for 12 month
  • 55. „… suggest that vitamin D repletion in patients with PHPT does not exacerbate hypercalcemia and may decrease levels of PTH and bone turnover“. Grey et al. JCEM 2005
  • 56. ? Mechanisms
    • PTH-induced increase in 1-alpha hydroxylase
    • ↑ 1,25(OH) 2 D (calcitriol)
    • inhibition of PTH gene transcription, protein production and parathyroid gland proliferation (Beckermann Am J Med Sci 1999)
    • no association between change in 1,25(OH) 2 D and PTH levels (Grey JCEM 2005)
    • no decrease of PTH with active Vit D metabolites (Lind Acta Endocrinol 1989)
    • no relation 25(OH)D with 1,25(OH) 2 D in cross-sectional studies (Silverberg Am J Med 1999, Rao JCEM 2000)
  • 57. Mechanisms
    • ? non- 1,25(OH) 2 D induced effects of 25(OH)D and other metabolites on PTH production
    • ? stimulation of VitD receptor in parathyroid tissue by VitD deficiency
    • ? intracrine action of parathyroid-derived 1,25(OH) 2 D to reduce PTH
  • 58. Interactions with magnesium low magnesium levels blunt the stimulation of parathyroid glands induced by low Vit D levels often normal PTH levels even when 25-OH VitD below 20 ng/mL unknown effects of hypomagnesia in patients with pHPT Sahota et al. Osteoporos Int 2006
  • 59. Further secrets parathyroid
    • PTH levels normally decrease with age
    • association pHPT with metabolic syndrome
      • increased body weight in patients with pHPT (Bolland JCEM 2005, Meta-analysis)
      • increased leptin and decreased adiponectin (Delfini et al Metabolism 2007)
    • consider co-existing disorders in patients with pHPT
      • drugs (thiazides, lithium), malabsorption, renal failure, tumours
  • 60. Familiar hypocalciuric hypercalcaemia (FHH)
    • 2% of all asymptomatic hypercalcaemia
    • dominantly inherited
    • usually heterozygous loss of function mutation in the CaSR
    • PTH inappropriately normal or high, lifelong Ca ++ ↑ and Mg ++ ↑ , both of variable degree
    • enlarged glands and mild parathyroid hyperplasia can occur
  • 61. FHH
    • usually benign and asymptomatic
    • family history?
    • urinary calcium/creatinine clearance < 0.01
    • surgery in FHH patients without benefit!
  • 62.  
  • 63. Patient with adynamia and dizziness
    • bradycardia
    • first degree AV block
    • low voltage in all leads
    • flat or negative T-waves
    • ↑ QT interval
  • 64. ECG in severe hypothyroidism after starting treatment with L-Thyroxine untreated
  • 65. Conclusions
    • patients with neck hormonal derangements may primarily present in other Specialties
      • e.g. Gastroenterology, Orthopaedics, ED, Cardiology, Psychiatry
    • being unaware of hormonal derangements can expose the patient to unnessecary procedures
      • e.g. EGD, coloscopy, intracardiac catheter, surgery…