style="font-size:15px;"> 6 Thyroid function test.7 Urinary sodium and osmolality.
8 Water deprivation test.
1 35. A 76‐year‐old woman presents with confusion. Her family reports her being constipated and gaining 5 kg weight in recent months. On examination, she is alert but disoriented in time and place. Her HR is 52 bpm and BP is 158/95 mmHg. There is non‐pitting oedema in the bilateral low limbs. The CXR reveals cardiomegaly and bilateral small pleural effusions. Apart from mild hyponatraemia (serum sodium level 133 mmol/L), other biochemistry results are unremarkable. What is the next most appropriate investigation?
2 36. A 68‐year‐old woman presents after a two‐day history of vomiting. She is found to have hypernatraemia but her elevated serum sodium concentration did not improve despite adequate fluid replacement. She has history of bipolar disorder and has been taking lithium for the past 8 years. What is the appropriate investigation after stabilizing this patient clinically?
Answers
1. Answer: D
This patient has typical clinical features of acromegaly. She has elevated insulin like growth factor 1 (IGF‐1) and growth hormone (GH) levels. The MRI demonstrates a large pituitary tumour. There is NO need for further investigation. She needs referral for neurosurgery.
Acromegaly is a severe disease resulting from GH hypersecretion, usually caused by a pituitary adenoma. It is associated with cardiovascular, cerebrovascular, and respiratory disorders, malignancies, and a high mortality. The onset of acromegaly in adults is usually insidious. Typical physical examination findings include hand and foot enlargement, facial bone enlargement and acral/soft tissue changes.
Investigation in a suspected patient involves measurement of IGF‐1 and GH. Elevated IGF‐I levels in a patient with clinical features of acromegaly almost always indicate GH excess. In subjects with elevated or equivocal serum IGF‐1 concentrations, guidelines recommended confirmation of the diagnosis with a lack of suppression of GH to less than 1 mcg/l following an oral glucose load. In a patient with signs and symptoms of acromegaly and a clearly elevated IGF‐1 value, an oral glucose suppression test is not needed for diagnosis.
GH, produced by the somatotroph cells of the pituitary gland in a pulsatile fashion, circulates and stimulates hepatic secretion of IGF‐1. A random GH measurement is not useful in diagnosis because of the lack of a well‐defined normal range, although a markedly elevated random GH level is consistent with the disease.
After biochemical diagnosis of acromegaly, imaging studies are needed; a MRI scan of the head is the preferred modality and should be obtained to determine tumour size, location, and invasiveness. Visual field testing is performed if the tumour is touching or compressing the optic chiasm. A thorough ophthalmologic examination should be performed if the patient describes diplopia and the tumour is invading the cavernous sinus. Further endocrine testing is also necessary to determine general pituitary function and need for hormone replacement therapy.
Acromegaly is associated with diabetes, hypertension, OSA, and cardiovascular disease. There is also increased risk for colonic polyps and colonoscopy is indicated when acromegaly is diagnosed. Excess GH is also associated with an increase in thyroid nodules and thyroid cancer. A thyroid ultrasound may be performed if there is palpable thyroid nodularity.
The goals of therapy for acromegaly are to normalise GH and IGF‐1 activity, reduce tumour size, prevent local mass effects, reduce signs and symptoms of disease, prevent or improve medical comorbidities, and prevent premature mortality. Surgery is the treatment of choice. Surgery is useful to debulk or resect the somatotroph adenoma, decompress local mass effects, and rapidly lower or normalise GH and IGF‐1 values.
Surgery is recommended for all patients with microadenomas, and in experienced hands >85% are curable. Surgery is also recommended for all patients with macroadenomas and mass effects. Surgical cure rates for macroadenomas range from 40–50%, likely reflecting the high prevalence of extrasellar extension and parasellar invasion of the cavernous sinus. The transsphenoidal approach is the most common procedure, with craniotomy reserved for select cases involving large, extrasellar lesions. Transnasal endoscopic endonasal procedures offer improved visibility and are rapidly replacing microscopic transsphenoidal techniques.
Medical therapy is largely used in an adjuvant role for patients with residual disease following surgery. However, primary medical therapy may be considered in subjects with macroadenomas and extrasellar involvement (especially involving the cavernous sinus) but no evidence of local mass effects such as chiasmal compression. In this situation, surgery will unlikely be curative and primary medical therapy in lieu of surgery may be considered. Primary medical therapy may also be considered in patients, who are at high risk from surgery and according to patient preferences. In a patient who is undergoing primary medical therapy, surgery can always be reconsidered for tumour debulking to improve response to medical therapy. Somatostatin receptor ligands (SRLs) such as octreotide are the mainstay of medical treatment. Octreotide acts primarily on somatostatin receptor subtypes II and V, inhibiting GH secretion. Dopamine agonist such as cabergoline can also be used. Cabergoline monotherapy results in biochemical control rates of approximately 35%; similar benefits have also been seen with the addition of cabergoline to an SRL in patients with inadequate control on SRL therapy. GH receptor antagonist, pegvisomant monotherapy administered as second‐line therapy yields biochemical control rates of 90% or more in clinical trials and closer to 60% in real‐world surveillance studies. Radiation therapy is largely relegated to an adjuvant role.
Melmed, S., Bronstein, M., Chanson, P., Klibanski, A., Casanueva, F., Wass, J., Strasburger, C., Luger, A., Clemmons, D. and Giustina, A. (2018). A Consensus Statement on acromegaly therapeutic outcomes. Nature Reviews Endocrinology, 14(9), pp.552–561.
https://www.nature.com/articles/s41574-018-0058-5
2. Answer: C
The patient is likely to have a diagnosis of adrenal crisis with symptoms of nausea, vomiting, hypotension, severe lethargy, weakness, altered mental state, hyponatraemia, hyperkalaemia, and a known history of adrenal insufficiency. Her low BP suggests that she has adrenal crisis with haemodynamic instability, rather than adrenal insufficiency. Septic shock can clinically mimic adrenal insufficiency with symptoms of hypotension, fever, and gastrointestinal symptoms, thus it is important not to miss either the diagnosis of sepsis or adrenal crisis and initiate appropriate investigations and treatment. Administration of appropriate dosage of corticosteroids is imperative to avoid adverse sequalae.
In patients with vomiting and diarrhoea, administration of 100 mg IV hydrocortisone initially is recommended followed by IV hydrocortisone 100 mg qid then 50 mg qid the next day until it is safe to change to oral hydrocortisone after 24 hours. Oral hydrocortisone is usually prescribed at 2 to 3 times the normal oral hydrocortisone dose, with a gradual taper back to the patient's regular dose over the following 2 to 3 days. Administration of oral fludrocortisone is not required if the initial hydrocortisone doses exceed 50 mg over 24 hours for patients with primary adrenal insufficiency as high doses of hydrocortisone will exert mineralocorticoid activity. Oral fludrocortisone can be resumed once the patient is able to have oral hydrocortisone.
Biochemical abnormalities observed in patients with adrenal crisis include hyponatraemia, hyperkalaemia, hypercalcaemia, hypoglycaemia, neutropenia, lymphocytosis, eosinophilia, and mild normocytic anaemia. IV fluid
