Diagnosis and Management of Adrenal Failure: The Short Synacthen® Test

Adrenal failure is a condition characterized by multiple signs and symptoms and abnormal biochemistry. The diagnosis of adrenal failure is established by a failure of the plasma cortisol concentration to increase in response to adrenocorticotropic hormone (ACTH). The short corticotropin test is the gold standard diagnostic tool for this condition. If this test is not possible, an initial screening procedure comprising the measurement of morning plasma ACTH and cortisol levels is recommended. Diagnosis of the underlying cause should include a validated assay of autoantibodies against 21-hydroxylase. Treatment involves once-daily fludrocortisone and hydrocortisone or prednisolone. Follow-up should aim at monitoring appropriate dosing of corticosteroids and associated autoimmune diseases, particularly autoimmune thyroid disease. Serum urea and ESR may not be diagnostic, while serum calcium and thyroid function tests can be abnormal in untreated Addison’s disease. This article discusses the diagnosis and management of adrenal failure, with a focus on the short Synacthen® test.

The Importance of Self-Monitoring Blood Glucose in Diabetes Management

Self-monitoring of blood glucose is a crucial aspect of diabetes management. According to the National Institute of Clinical Excellence (NICE) guidelines, blood glucose should be checked at least four times a day, including before each meal and before bed. More frequent monitoring is recommended during periods of illness and before, during, and after sport. Blood glucose targets should be 5-7 mmol/l on waking and 4-7 mmol/l before meals and at other times of the day. Additionally, glycosylated haemoglobin (HbA1c) levels should be checked every 3-6 months with a target of 48 mmol/mol (6.5%) or lower. Checking blood glucose only during illness or once a day is not recommended as it can lead to complications such as hypoglycaemia and hyperglycaemia. Regular self-monitoring of blood glucose is essential for good diabetes management.

NICE updated its guidance on the management of type 2 diabetes mellitus (T2DM) in 2022, reflecting advances in drug therapy and improved evidence regarding newer therapies such as SGLT-2 inhibitors. The first-line drug of choice remains metformin, which should be titrated up slowly to minimize gastrointestinal upset. HbA1c targets should be agreed upon with patients and checked every 3-6 months until stable, with consideration for relaxing targets on a case-by-case basis. Dietary advice includes encouraging high fiber, low glycemic index sources of carbohydrates and controlling intake of foods containing saturated fats and trans fatty acids. Blood pressure targets are the same as for patients without type 2 diabetes, and antiplatelets should not be offered unless a patient has existing cardiovascular disease. Only patients with a 10-year cardiovascular risk > 10% should be offered a statin, with atorvastatin 20mg as the first-line choice.

Insulin-dependent diabetes patients rely on insulin to regulate their blood glucose levels. Without insulin, several physiological changes occur. However, these changes do not happen immediately. Here are some effects of insulin absence in insulin-dependent diabetes patients:

Unchanged HbA1c levels – Correct: HbA1c levels do not change significantly over two to three days without insulin. Changes in HbA1c levels are observed over weeks and months.

Below normal fatty acid levels – Incorrect: In the absence of insulin, triglyceride hydrolysis and increased release from adipose tissue occur, giving raised fatty acid levels. Fatty acids are utilised to synthesise ketones.

Below normal glucagon levels – Incorrect: The body responds to the absence of insulin by increasing glucagon levels. In a healthy individual, this raised glucagon would raise glucose levels in the bloodstream, providing target organs with utilisable glucose. However, in a diabetic patient, the absence of insulin means target organs are still not able to utilise this resource.

Hypoglycaemia – Incorrect: In the absence of insulin, hyperglycaemia would be expected to develop. Ketones are generated by the body as an alternative energy source to glucose, since to utilise glucose, insulin is required.

Undetectable ketones – Incorrect: A diabetic patient who is normally dependent on insulin is at risk of developing diabetic ketoacidosis (DKA) even with only a weekend of missed insulin doses.

Endocrine Disorders: Addison’s Disease, Cushing Syndrome, and Conn Syndrome

Addison’s Disease:
Addison’s disease, or primary hypoadrenalism, is a condition characterized by chronic adrenal insufficiency. It is most commonly caused by autoimmune destruction of the adrenals in the UK, while tuberculosis is the most common cause worldwide. Other causes include long-term exogenous steroid use, cancer, or hemorrhage damage. Symptoms develop gradually, but patients can present in Addisonian crisis if there is a sudden deterioration in adrenal function or a physiological stress that the residual adrenal function cannot cope with. Treatment is with long-term replacement of corticosteroids and aldosterone.

Cushing Syndrome:
Cushing syndrome is a result of excess corticosteroid. It can be caused by exogenous steroids, primary hyperadrenalism, or secondary hyperadrenalism. Signs and symptoms include weight gain with moon facies and buffalo hump, hypertension, hyperglycemia, mood changes, hirsutism, baldness, and sleep disturbance.

Conn Syndrome:
Conn syndrome, also known as primary hyperaldosteronism, is caused most commonly by adrenal hyperplasia or adenomas. It results in excess aldosterone release, causing difficult-to-treat hypertension, hypernatremia, and hypokalemia.

Other Disorders:
Hypoglycemia occurs in insulinoma, but the other features are absent. Peutz-Jeghers syndrome is an autosomal dominant condition characterized by perioral freckling and small bowel polyps, which may present with vomiting secondary to intussusception from the small polyps but does not explain the hypoglycemia.

Differentiating Causes of Thyrotoxicosis: A Brief Overview

Thyrotoxicosis, or hyperthyroidism, can be caused by various conditions, including Graves’ disease, De Quervain’s thyroiditis, Hashimoto’s thyroiditis, hypothyroidism, and toxic multinodular goitre. Among these, Graves’ disease is the most common cause, characterized by autoimmune dysfunction and typical hyperthyroid symptoms. About a third of patients with Graves’ disease also develop eye signs, while pretibial myxoedema or clubbing of the fingers may occur rarely. De Quervain’s thyroiditis, on the other hand, is associated with transient hyperthyroidism following a viral infection and neck pain. Hashimoto’s thyroiditis, an autoimmune condition, causes hypothyroidism instead of hyperthyroidism. Hypothyroidism presents with weight gain, fatigue, constipation, dry skin, and depression, and is characterized by raised TSH and reduced T4 or T3. Finally, toxic multinodular goitre is the second most common cause of hyperthyroidism in the UK, presenting with a multinodular goitre and hyperthyroidism without Graves’ disease symptoms. However, in the case presented, the positive TPO antibodies and typical Graves’ disease symptoms make it the most likely diagnosis.

The TFTs indicate a diagnosis of hypothyroidism, which can be treated with levothyroxine. Carbimazole is not suitable for this condition as it is used to treat hyperthyroidism. To ensure proper absorption, levothyroxine should be taken 30 minutes before consuming food, caffeine, or other medications.

Managing Hypothyroidism: Dosage, Monitoring, and Side-Effects

Hypothyroidism is a condition where the thyroid gland does not produce enough thyroid hormone. The main treatment for hypothyroidism is levothyroxine, a synthetic form of thyroid hormone. When managing hypothyroidism, it is important to consider the patient’s age, cardiac history, and initial starting dose. Elderly patients and those with ischaemic heart disease should start with a lower dose of 25mcg od, while other patients can start with 50-100mcg od. After a change in dosage, thyroid function tests should be checked after 8-12 weeks to ensure the therapeutic goal of normalising the thyroid stimulating hormone (TSH) level is achieved. The target TSH range is 0.5-2.5 mU/l.

Women with hypothyroidism who become pregnant should have their dose increased by at least 25-50 micrograms levothyroxine due to the increased demands of pregnancy. The TSH should be monitored carefully, aiming for a low-normal value. It is important to note that there is no evidence to support combination therapy with levothyroxine and liothyronine.

While levothyroxine is generally well-tolerated, there are some potential side-effects to be aware of. Over-treatment can lead to hyperthyroidism, while long-term use can reduce bone mineral density. In patients with cardiac disease, levothyroxine can worsen angina and lead to atrial fibrillation. It is also important to be aware of drug interactions, particularly with iron and calcium carbonate, which can reduce the absorption of levothyroxine. These medications should be given at least 4 hours apart.

In summary, managing hypothyroidism involves careful consideration of dosage, monitoring of TSH levels, and awareness of potential side-effects and drug interactions. With appropriate management, patients with hypothyroidism can achieve normal thyroid function and improve their overall health.

Endocrine Disorders and Their Clinical Presentations

Acromegaly, Cushing’s syndrome, hyperprolactinaemia, hyperthyroidism, and multiple sclerosis are all endocrine disorders that can present with various clinical features. Acromegaly is caused by excess growth hormone secretion and can lead to enlarged hands, coarse facial features, and bitemporal hemianopia. Cushing’s syndrome may present with central obesity, muscle atrophy, and osteoporosis, but visual dysfunction is not typical. Hyperprolactinaemia can cause amenorrhoea or oligomenorrhoea, infertility, and galactorrhoea, but this presentation more closely fits with acromegaly. Hyperthyroidism may present with weight loss, tremor, and heat intolerance, but bitemporal hemianopia is not typical. Multiple sclerosis is a chronic inflammatory demyelination of the central nervous system and can present with various symptoms, but this patient’s presentation does not fit with features of multiple sclerosis.

The patient is experiencing hyperthyroidism due to an excess of levothyroxine replacement. It is important to reduce the dose of levothyroxine and monitor the patient with regular blood tests until they become euthyroid again. Starting carbimazole or increasing the dose of levothyroxine is not recommended as it could lead to further complications. Propylthiouracil is only used in cases of thyrotoxic storm and radio-iodine therapy is not necessary in this case as the hyperthyroidism is due to over-replacement of levothyroxine.

Diagnosing Cranial Diabetes Insipidus: A Pituitary Tumour as the Likely Cause

Cranial diabetes insipidus (DI) is a condition where the kidneys are unable to reabsorb free water, resulting in excessive water loss. The most likely cause of this condition is reduced antidiuretic hormone (ADH) secretion, which can be caused by a pituitary tumour. In this case, the patient’s low urine osmolality and reduced response to the water deprivation test confirm the presence of cranial DI.

Chronic renal disease and lithium therapy can also cause nephrogenic DI, but the patient’s response to desmopressin im excludes these as potential causes. Diabetes mellitus may cause polydipsia and polyuria, but it also presents with glycosuria and hyperglycaemia. Primary polydipsia, characterized by a compulsive desire to drink, can cause low urine osmolality, but the patient’s ability to concentrate urine to some extent excludes this as a likely cause.

In conclusion, a pituitary tumour is the most likely cause of the patient’s cranial DI, as confirmed by the water deprivation test and response to desmopressin im.