Endocrinology
Overview
Cushing’s syndrome is caused by an inappropriate and chronic exposure to excessive levels of cortisol. The source of this excess of cortisol can be endogenous or exogenous.1 When the excess of cortisol is caused by a pituitary adenoma (i.e. a tumour of the pituitary gland located in the brain), the condition of the patient is defined as Cushing’s disease.1
Because other conditions share the same signs and symptoms, Cushing’s syndrome can be difficult to diagnose (particularly endogenous Cushing’s syndrome), with a time to diagnosis of more than 6 years.2
Cushing’s syndrome affects less than 1 in 10,000 people in the European Union. Females are more frequently affected than males, and represents 75% of the Cushing’s syndrome population.3
The well accepted treatment goal for patients is to normalise cortisol levels. Typical treatments include surgery and/or medical interventions. With proper treatment, the progression of the disease can be halted and symptoms reduced.4
Diagnosis
The first step of Cushing’s syndrome diagnosis is to check the medications a patient takes. Then, the second step consists of a variety of tests, including:1
- The measurement of urinary free cortisol level that will show if the body is producing too much cortisol. Urine can be collected over a 24h period.
- Late night salivary cortisol: In people without Cushing’s syndrome, cortisol level drop significantly in the evening. If this level is too high late at night, doctors might suspect a Cushing’s syndrome.
- Dexamethasone suppression test (DST) is also typically used to diagnose Cushing’s syndrome.
Symptoms
Patients with Cushing’s syndrome may develop the following signs and symptoms, which can vary from one patient to another:5
- Rapid weight gain,
- Central obesity,
- Emotional instability and depression,
- Severe fatigue and weakness,
- Osteopenia (low bone density),
- Dyslipidaemia (blood lipid levels that are too high or low),
- Moon face (medical sign in which the face develops a rounded appearance),
- Hirsutism (i.e. excessive facial or body hair growth),
- Striae,
- Buffalo hump,
- Irregular menstruation in women,
- Acne.
Causes
Cushing’s syndrome can have either endogenous or exogenous origin (i.e. medication). Endogenous Cushing’s syndrome is due to an excess in cortisol production. In normal conditions, ACTH (adrenocorticotropic hormone) is secreted by the pituitary gland to stimulate the release of cortisol from the adrenal glands (located above the kidney).
There are 3 different causes of endogenous Cushing’s syndrome:
- In pituitary Cushing’s, also known as Cushing’s Disease, a pituitary adenoma induces an excessive production of ACTH, leading to an increased production of cortisol, and this represents 70% of endogenous Cushing’s syndromes,
- In adrenal Cushing’s, the increased production of cortisol is caused by an adrenal gland tumour,
- In diseases such as small cell lung cancer, ACTH can be produced outside the pituitary-adrenal system and affect the production of cortisol,
Exogenous Cushing’s syndrome (or iatrogenic) is caused by the use of glucocorticoids (for instance Prednisone) to treat other diseases (like asthma).
References
- Nieman LK, Biller BMK, Findling JW, et al. The diagnosis of Cushing’s syndrome: an Endocrine Society Clinical Practice Guideline. Journal of Clinical Endocrinology & Metabolism. 2008;93(5):1526-1540.
- Pivonello R, De Leo M, Cozzolino A, Colao A. The treatment of Cushing’s disease. Endocrine Reviews. 2015;36(4):385-486.
- Orphanet. Cushing’s syndrome. Orphanet encyclopedia.
- Nieman LK, Biller BMK, Findling JW, et al. Treatment of Cushing’s syndrome: an Endocrine Society Clinical Practice Guideline. Journal of Clinical Endocrinology & Metabolism. 2015;100(8):2807-2831.
- Newell-Price J, Bertagna X, Grossman AB, Nieman LK. Cushing’s syndrome. The Lancet. 2006;367(9522):1605-1617.
Overview:
Acromegaly is a rare hormonal disorder characterised by an over-production of Growth Hormone (GH) by the pituitary gland1. The pituitary gland is an endocrine gland located at the base of the brain involved in the synthesis of several hormones including GH.2
The first symptom of this disorder is the abnormal growth of the hands and feet and more generally an increase of the bones size3. Even though Acromegaly can develop at any age, it usually affects middle-aged women and men.1
Because Acromegaly is uncommon and physical changes occur very slowly, the condition sometimes takes from 5 to 6 years to be diagnosed and can lead to severe complications such as severe damage to the joints and problems affecting the cardiovascular and respiratory systems.1
In Europe, Acromegaly affects approximately 5.9 in 10,000 people.4
The most well accepted treatment goal is to target the source of the Growth Hormone over production. Typical treatments include surgery and/or medical treatment. With proper medical treatment, the progression of the disease can be halted or symptoms reduced.1
Diagnosis:
Physicians most often diagnose Acromegaly by ordering two blood tests that help determine if the body is making too much GH. The first test measures the level of IGF-1 in the blood levels, a reliable way to track GH in the body. A high IGF-1 level suggests Acromegaly. The second test, a glucose tolerance test will confirm the diagnosis, as growth hormone levels and blood glucose levels are connected.5
If the blood tests confirm that the body is making too much GH, imaging tests will be conducted to locate and measure the tumour that may be causing the problem. The preferred test for viewing a pituitary tumour is magnetic resonance imaging (MRI).5
Symptoms:
Patients with Acromegaly may develop the following signs and symptoms:1
- Hands and feet become larger and swollen. There may be a change in ring or shoe size and width,
- Lips, nose, and tongue become larger,
- Enlarged facial features causing the lower jaw to protrude, nasal bone enlargement and teeth to space out,
- Oily, thickened and hairier skin,
- Excessive sweating,
- Deepening of the voice,
- Headaches,
- Problems with the vision,
- Heavy snoring,
- Daytime sleepiness.
Causes:
Acromegaly is characterised by a hypersecretion of Growth Hormone (GH) by the pituitary gland. The pituitary gland is an endocrine gland located at the base of the brain, which produces different hormones, including Growth Hormone.1
Growth Hormone stimulates growth, cell reproduction, cell regeneration and the production of insulin-like growth factor-1 (IGF-1) once released in the bloodstream. If too much GH is secreted, too much IGF-1 can lead to Acromegaly and gigantism.3
In 95% of cases, Acromegaly is caused by a non-cancerous tumour of the pituitary gland called a pituitary adenoma.6
References
- Fleseriu M, Langlois F, Lim DST, Varlamov EV, Melmed S. Acromegaly: pathogenesis, diagnosis, and management. Lancet Diabetes Endocrinol. 2022 Nov;10(11):804-826.
- Emerson, Charles H.. “pituitary gland”. Encyclopedia Britannica, 30 Oct. 2024, https://www.britannica.com/science/pituitary-gland. Accessed 4 November 2024
- Gigantism and Acromegaly. John D. Carmichael, MD, Keck School of Medicine of the University of Southern California. Reviewed/Revised Apr 2023. URL: Gigantism and Acromegaly – Hormonal and Metabolic Disorders – Merck Manual Consumer Version
- Crisafulli S, Luxi N, Sultana J, Fontana A, Spagnolo F, Giuffrida G, Ferraù F, Gianfrilli D, Cozzolino A, Cristina De Martino M, Gatto F, Barone-Adesi F, Cannavò S, Trifirò G. Global epidemiology of acromegaly: a systematic review and meta-analysis. Eur J Endocrinol. 2021 Jul 1;185(2):251-263
- Giustina A, Biermasz N, Casanueva FF, Fleseriu M, Mortini P, Strasburger C, van der Lely AJ, Wass J, Melmed S; Acromegaly Consensus Group. Consensus on criteria for acromegaly diagnosis and remission. Pituitary. 2024 Feb;27(1):7-22.
- Zahr R, Fleseriu M. Updates in Diagnosis and Treatment of Acromegaly. Eur Endocrinol. 2018 Sep;14(2):57-61. doi: 10.17925/EE.2018.14.2.57.
