Category Archives: Endocrinology

Prolactin

Endocrinology, General paediatrics, Neurology

Secreted from the anterior pituitary (along with growth hormone, ADH, ACTH, TSH, FSH/LH), but also a stress hormone (can be used to distinguish pseudo seizures from epileptic seizures). So can go up to 1000 in healthy people. Always worth repeating a high result at least 24hrs hours later, after a 20 minute rest.

Important because of prolactinomas, which can cause:

  • gynaecomastia
  • galactorrhoea
  • delayed puberty
  • space occupying lesion effects – headaches, visual field defects

Any lesion in the vicinity of the pituitary may also cause raised prolactin so not specific.

High levels can also be due to presence of “macroprolactin“, antibody complex polymers without biological action – usually less than 30% of the total – lab can check and give true monomeric value.

Hypertension

Cardiology, Endocrinology, General paediatrics, OPD, Renal

In children under 10, high BP is usually secondary to an underlying disease or condition. Primary hypertension increasingly recognised in older, obese children.

Do repeated measurements, ideally automated home BP monitoring, before diagnosing hypertension. Check manually as well as with automated device. Beware “white coat effect”, even if not clearly anxious.

Use appropriate cuff size – cuff should cover at least 75% of the upper arm from the acromion to the olecranon (should be sufficient space at the antecubital fossa to apply stethoscope!) .  An inappropriately small cuff will overestimate BP.

Long list of causes, so follow the clues.

Family history important, of course.

Examination

So needs thorough history and examination, including:

  • Fundi
  • Bruits, radiofemoral delay
  • Neck for goitre

Complications

Consider then end organ effects –

  • Proteinuria, high creatinine
  • Retinopathy
  • Left ventricular hypertrophy, cardiac failure
  • Abnormal tone and reflexes, cranial nerve deficits if severe

Management

Depends on how high, whether other risk factors (diabetes, chronic kidney disease), symptoms and evidence of end organ damage.

Initially low salt diet, weight loss (if obese).  Remember other morbidities related to obesity.

Acute hypertension might need frusomide and/or nifedipine.

Long term treatment is only going to be started if no improvement with lifestyle measures. Target BP depends on risk factors, as above.

[2016 European Society for Hypertension guidelines]

Short Stature

Endocrinology, General paediatrics, OPD

Are they really? Plot height and weight, and check figures if in doubt!

Investigate if:

  • Severe short stature = height below the 0.4th centile
  • Height more than 2 centile spaces below the mid-parental height
  • Downwards crossing of more than 1 height centile in 1 year, in a child aged 2 years or over

Is there evidence of chronic disease? Needs full history and examination, including urine dip. Common things would be renal failure, coeliac disease, IBD, hypothyroidism. Endocrine causes tend to produce relatively heavy children, other chronic diseases tend to produce relatively slight children.

Brain tumour symptoms?

Are they dysmorphic? Is one parent dysmorphic? Main syndromes to look out for:

  • Turners – besides short stature, webbed neck, characteristic facies, short metacarpals, broad chest with widely spaced nipples, hyperconvex fingernails and toenails (but can be missed); decreased growth velocity and delayed puberty
  • Short limbs – SHOX mutations eg Leri-Weill dyschrondeostosis but milder variants. Classically mesomelia (short proximal bones) and Madelung deformity (wrist) but these may only become obvious in later childhood.
  • Achondroplasia or hypochondroplasia (FGFR3 (Fibroblast Growth Factor Receptor 3) mutations)

Bone age will be delayed in all except familial and idiopathic. Progressively falls behind in endocrine disorders.

Causes

Constitutional delay – good weight at birth, then “catch down” growth, dropping through centiles in infancy. Growth velocity is then normal, but with delayed bone age and delayed puberty.

Small for gestational age babies tend to catch up in first few years of life with their genetic potential, but can take up 4 years or more. 10% however remain small (more than 2 SDs below MPH) through life. Consider other causes if no catch up in first 6 months of life or still small at 2 years.

Growth hormone deficiency – can be congenital or acquired (head injury, meningitis etc). Early growth tends to be normal (growth hormone doesn’t contribute much in first few years of life). Look for hypoglycaemia in neonatal period, microphallus, midline facial abnormalities.

Investigations

  • Karyotype if dysmorphic or if girl
  • TFTs
  • IGF1 – screening test for Growth hormone problems, but may need GH stimulation testing as limited reference ranges in under 2s
  • FBC, U&Es, LFTs, Vit D, Ferritin
  • TTG antibody
  • LH/FSH, testosterone, oestradiol if pubertal signs
  • Urinalysis
  • Bone age if thinking constitutional
[SPEG Guideline]

Autoimmune hypothyroidism

Endocrinology, General paediatrics

Associated with other autoimmune conditions, of course, especially diabetes , Addisons and coeliac disease.

If high TSH and low T4, goitre and positive TPO antibodies, then diagnosis clear.

Isolated high TSH is seen with some drugs and after acute illness. Persistently high TSH and normal T4 might be subclinical hypothyroidism. Treatment is recommended if symptoms/signs, especially if TPO positive as likely to become hypothyroid at some point anyway (pregnancy and infertility are other indications).

If TPO neg and no signs/symptoms, USS can be useful just to confirm evidence of thyroiditis.

Funny results are seen with TFT testing sometimes, appears to be interference of some kind – repeat with a different lab! Do T3 as well.

Management otherwise same as congenital hypothyroidism. Maintain TSH at any point within reference range unless symptomatic (RCT of aiming for lower limit did not show any benefit, plus risk of adverse effects). 

In adults, treat hypothyroidism if two TSH results over 10 – but consider also symptoms.  For lower levels, consider 6/12 trial of treatment.

Polycystic ovary syndrome (PCOS)

Endocrinology, General paediatrics, OPD

No single test. Polycystic kidneys are a common incidental finding at USS, so not sufficient for diagnosis.  Also operator dependent esp teens.

  • Hirsutism (even male pattern baldness), But NOT virilisation (eg clitoromegaly, voice changes, musculature).
  • acne (moderate to severe),
  • irregular periods.  Can be amenorrhoeic, dysfunctional uterine bleeding, infertility but 20% have normal cycle.
  • Obesity (35-50%, not all),
  • Acanthosis nigricans.

Insulin resistance is associated, and obviously presents the most important long term risk. Acanthosis nigricans is highly associated with insulin resistance, family history of type 2 or gestational diabetes a clue.

Differential includes pregnancy, hypothyroidism, hyperprolactinaemia (mild hyperprolactinaemia commonly seen in PCOS, transient), late onset Congenital Adrenal Hyperplasia (CAH), ovarian/adrenal tumour, Cushing syndrome.

Investigations

  • LH/FSH – ratio often high (3:1 or more) but inconsistent so not considered diagnostic
  • Testosterone can be high (up to 4.8) – if higher, suggests alternative diagnosis
  • Free androgen index (=testosterone x100/SHBG) can be high but our lab only calculates for adults – reference range of up to 7
  • SHBG – low in PCOS (and in obesity, hypothyroidism, hyperprolactinaemia). Plus marker of insulin resistance),
  • Prolactin, 17OH Progesterone for differential
  • Fasting glucose/insulin ratio (under 4.5=insulin resistance, up to 7 in adolescents), glucose tolerance test, lipids.

Manage symptoms (for young people hirsutism, adults infertility) and long term risk viz diabetes and cardiovascular disease.

Note that less than 4 menses per year has higher risk of endometrial cancer.

Consider:

  • oral contraceptive pill (OCP) – progesterone only, or combined, or else 12 week cycles of medroxyprogesterone acetate 5mg BD followed by 1 week break – NOT contraceptive!
  • Metformin
  • Spironolactone (has anti androgen effect)
  • Plucking/shaving/electrolysis/laser, eflornithine cream
  • Clomiphene for fertility.

[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1069067/]

Thyroid

Endocrinology, General paediatrics

Thyroid issues can be congenital, neonatal, autoimmune, or related to syndromes eg Downs, Digeorge.

Note that thyroid function tests can be affected by intercurrent illness, there is also viral thyroiditis where you might get transient (usually mild) abnormalities.  So borderline results (especially if asymptomatic or other medical issues) usually just need repeated.  If results confusing, do T3.  If normal then abnormal T4 likely to be transient.  If suspicion of evolving problem, do autoantibodies (TPO antibody, Thyroid Receptor Ab (TRab)).  If progressive decline then likely to be emerging autoimmune condition.

All kinds of unusual clinical presentations in thyroid disease, for example:

  • Effusions in hypothyroidism, including pericardial effusions – capillary dysfunction!? Impaired lymphatic drainage?
  • Body pain
  • Precocious puberty (although delayed more typical)

Congenital Hypothyroidism

Endocrinology, General paediatrics

Isolated TSH elevation >20 is usually treated.

True congenital hypothyroidism mostly dysgenesis, ie poorly formed gland, of which <2% have identified mutations (mostly thyroid peroxidise, thyroglobulin and TSH receptor proteins – EDTA sample, Dr Therese Bradley at SGH Genetics).  May be due to dyshormonogenesis (10%, autosomal dominant, gland looks normal on scan), TSH Receptor defect. Do a Family History.

Mostly found on newborn screening now.  Life long.

Placental thyroxine important, iodine too, on neonatal thyroid function.  In the first 14/7 of life, high TSH/T4/T3 seen.  Transient neonatal hypothyroidism seen, 25% of +ve guthrie tests!

Symptoms

If missed or untreated, classic signs are umbilical hernia, goitre, hoarse cry, coarse facies, Developmental Dysplasia of Hip!

Imaging

SPEG recommend that all families should be given the opportunity for imaging, subject to availability, because more informative than blood tests alone, will aid in genetic counselling, likelihood of lifelong treatment if proven permanent CH, provides a useful guide as to thyroxine dose.

Combined isotope and ultrasound imaging (dual scanning) is preferred. Isotope scans should be performed by day 5 of start of treatment to ensure avoidance of false negatives due to TSH suppression (advisable to take thyroid function sample on day of scans to confirm reliability of results). Ultrasound may show an abnormal gland (dyshormonogenesis) or else agenesis (no gland).   But in agenesis may be remnants of embryonic structural elements which can be mistaken for a gland – can persist into teenage years but max 5mm x 5mm! Hence importance of supporting radio-isotope imaging.  Experience of ultrasonographer important.

Management

Some concern that thyroxine liquid not as consistent levels?  Automatic script request from pharmacy, patient then notified when ready.

Repeat TGTs at 10-12 weeks.  Aim to keep TSH in lower half of reference range (room to spare as child grows).

Follow up

  1. Scottish guideline suggests typical doses at different ages, up to age 3, to encourage dose changes with growth rather than waiting till dose insufficient and hypothyroidism emerges (see table).  Use TFTs to confirm compliance.
  2. Assess growth: weight, length until 2 years, then height, head circumference until 3 years
  3. Assess development – consider pre-school audiology (for subtle hearing impairment due to CH)
  4. Transition – patient education. Boys to GP (unless problems with control), girls – to adult endocrinology (for pre-pregnancy counselling).

Aim for fT4 > 15 pmol/l and TSH <5.0 mU/l

Age LT4 dose (ug daily) LT4 dose (ug/kg/day)
Female Male Female Male
3 months 41.3 43.3 7.2 6.9
6 months 45.8 50.0 6.1 6.2
9 months 47.9 53.1 5.6 5.7
12 months 55.0 53.1 5.8 5.2
18 months 62.5 61.1 5.8 5.3
24 months 70.3 58.3 5.9 4.6
36 months 75.0 62.5 5.3 4.25

Insulin pumps

Clinical, Endocrinology, General paediatrics

Pumps particularly good for recurrent hypoglycaemia, suboptimal control, under 5s, better QOL.

Good for sport.

Parents report loss of control!

Continuous blood glucose monitoring – 6 days, twice daily calibration bloods. Not Prescribable. Some link to pumps, others diagnostic only. Newest pumps can auto-adjust rate but only downwards. Esp normal pre-prandial bloods but Suspected hyperglycaemic between meals.

Ketones cause insulin resistance so higher doses acceptable. Blood ketone over 3 must come to hospital, but no fixed need for IV therapy.

Tight glucose from diagnosis seems to give best results in long term – “metabolic memory”? Prolonged honeymoon phase? Better education?

ADAPT study starting, prevention.

Only 15g snack allowed if on pen eg half apple! Else low carb eg cheese, pepperoni. Pumps allowed snacks of any size, tend to calm down after first couple of weeks!

Digestion v variable. High fat, high carb? Glycemic index ie fibre. Chewing!

Pump can bolus with individual courses! Slow bolus for cinema or buffet meal eg over 30 mins.

Non-waterproof pumps disconnected for bath etc, shower cap applies to cannula site, leave pump running to avoid air space.

 

 

Diabetic Ketoacidosis

Emergency medicine, Endocrinology, General paediatrics

DKA – BSPED guidance 2021.

The potentially serious acute complication of diabetes.  In the absence of adequate insulin, glucose levels start to rise in the blood, spilling over the threshold for kidney resorption and causing a diuresis.  Metabolism switches to ketone bodies, causing acidosis.

Presents with weight loss, tiredness, vomiting, heavy breathing (Kussmaul), reduced consciousness.  Diabetes symptoms of course, if first presentation, which might just be new wetting, or unusually heavy nappies.  Can be confused with pneumonia, or appendicitis! Often missed diagnosis.  In 2020 Lanarkshire audit, half had seen GPs at least once before diagnosis, with many having had bloods done rather than BM, or being asked to hand in urine the next day… 40% had BM done by family member!

Traditionally 15-17% of new presentations of diabetes are DKA, but with pandemic went up to 66%

ISPAD def DKA = Bicarbonate pH under 7.3 (H+50) PLUS ketones 3+ (blood or urine).

Beware can develop with normal glucose levels IN THOSE TAKING INSULIN.  Suspect if blood ketones above 3 in known diabetic, refer to hospital.  Between 0.5 and 3, follow sick day rules.

Mild (over 7.2 or 63) vs moderate (7.1-7.2 or 79) vs severe (79+) categories.  Treat as 5 vs 7 vs 10% dehydrated respectively.

All get 10ml/kg over 30 mins (assuming you start IV fluids) unless shocked (10/kg over 15 mins, repeat up to 40 then inotropes).

Maintenance fluids (0.9% NaCl with 20mmol KCl per 500ml bag) as per traditional formula (Holliday-Segar method) – 100ml/kg/d for under 10kg; 50ml/kg/d additionally for each kilo between 10-20kg; 20ml/kg/d for each kilo above that.

  • Calculate deficit as above. Subtract initial 10/kg bolus (but not shock boluses) and correct over 48hrs
  • ONLINE CALCULATOR (dka-calculator.co.uk) comes with disclaimer, gives fluid calculations but then prints out 16 pages which you don’t need! [KB]
  • Note SCOTSTAR has separate DKASupportDocument for those likely to need transfer

See graphic in BMJ 2016.

Complications

If acidosis not correcting, check cannula, check fluid calculations, consider sepsis.  Replace insulin syringe! Acidosis can also be caused by hyperchloraemia (hence Plasmalyte preferred at RHC – less chloride).

Risk of thromboembolism due to dehydration and immobility during recovery.

Cerebral oedema

25% mortality from cerebral oedema, 34% long term neurodisability.  Headache, irritability, agitation.  Posturing, focal neurology eg eye movements, pupil asymmetry.  Cushings triad – bradycardia, hypertension, breathing irregularity.

Hypertonic saline (2.7 or 3%, 2.5-5ml/kg over 10-15 mins) or mannitol (20%, 0.5-1g/kg over 15 mins), no preference.  

Switching

Stay on DKA pathway (and not transfer to subcutaneous insulin) until:

  • The patient has been reviewed by a Consultant, or paediatric diabetes team medical staff and
  • The patient has no evidence of dehydration has no nausea or vomiting for 6 hours, and
  • Has blood glucose less than 10mmol/l, and
  • The blood ketones have fallen below 0.9mmol/l

Diabetes

Endocrinology, General paediatrics, OPD

Updated NICE guidance 2016.  Characteristics:

  • random glucose >11,
  • polyuria, polydipsia,
  • excessive tiredness,
  • weight loss.

WHO 1999 criteria – fasting normally <5.6, >7 diagnostic.  Random >11 diagnostic (assuming there’s nothing sticky on the finger tested!!!).  Glucose tolerance test (starts with fasting level) 2hr level >11.1 diagnostic, 7.8-11.1 is impaired glucose tolerance.

False positives – infection, recent surgery, uncontrolled thyroid disorder, starvation.

Epidemiology

Increasing rates in Europe. Scotland rate second only to Scandinavia.  Marked increase in under 5s. Aiming for routine pump therapy within a few months.

Subtypes

Type 2 more often in S Asian, Hispanic, Afro-Caribbean.  Clue is raised c-peptide – as this is co-produced with insulin, it means there is still endogenous insulin being produced (and cleared at more consistent rate than insulin, so more reliable, esp if on exogenous insulin).  C-peptide also used to look for insulinoma or factitious hypoglycaemia.  May also predict glycaemia control, complications and response to hypoglycaemic agents.

LADY – latent autoimmune diabetes of the young. More common? Different HLA type. Antibody positive but insulin sensitive and slow progress.

MODY – inability to produce insulin but normal beta cells.  Eg KIR 6.2 mutations, within months of birth.

Management

Reduced ideal HbA1c target – 48mmol/l (6.5%).  

No DAPHNE for kids.

Multiple daily injections from diagnosis, with level 3 carbohydrate (CHO) counting education, blood ketone testing strips.  Other regimens eg BD, TDS only for where problems with compliance.  See also pumps.

NICE guidance now includes Type 2 – suspect if strong FH, obesity, black/Asian origin, minimal insulin requirements (<0.5u/kg after “partial remission phase”), evidence of insulin resistance (viz acanthosis nigricans).

BMJ NICE diabetes infographic

Optimal blood glucose range is 4-7 on waking and between meals; 5-9 after meals; 5+ when driving.  At least 5 tests per day recommended, more frequently during physical activity and illness.But take into account:

  • risk of hypoglycaemia;
  • competitive sports;
  • need to lose weight;
  • life goals (careers, exams, foreign travel);
  • any relevant co-morbidity.

Monitoring

Annual thyroid, hypertension, albuminuria checks from diagnosis; retinopathy testing from age 12.  Type 2 don’t need thyroid but do need dyslipidaemia.

School

Most schools happy to give insulin. But no legal requirement. Lancets for school retract into cartridge.

Self-Efficacy

Encourage ownership of meters etc, downloading at home. Over 14 to get access to SCI-DC, as adults.