Nelson's syndrome

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Nelson's syndrome
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Nelson's syndrome is a disorder that occurs in about one in four patients who have had both adrenal glands removed to treat Cushing's disease. [1] In patients with pre-existing adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas, loss of adrenal feedback following bilateral adrenalectomy can trigger the rapid growth of the tumor, leading to visual symptoms (e.g. bitemporal hemianopsia) and hyperpigmentation. [2] The severity of the disease is dependent upon the effect of ACTH release on the skin, pituitary hormone loss from mass compression, as well as invasion into surrounding structures around the pituitary gland. [2]

Contents

The first case of Nelson's syndrome was reported in 1958 by Dr. Don Nelson. [2] Within the past ten to twenty years, improvements have been made with identification and care for patients with Cushing's disease. Techniques such as pituitary radiation therapy, ACTH assay, transsphenoidal pituitary surgery, higher resolution MRIs, and sampling of the inferior petrosal sinus have allowed physicians to pursue routes for Cushing's syndrome therapy prior to consideration of bilateral adrenalectomy. [2]

Nelson's syndrome is also referred to as post adrenalectomy syndrome, a possible result of adrenalectomy performed for Cushing's disease. [3]

Symptoms and signs

The common symptoms include:[ citation needed ]

Cause

Common causes include bilateral adrenalectomy for the treatment of Cushing's disease, and hypopituitarism. [5] The onset of the disease can occur up to 24 years after a bilateral adrenalectomy has been performed, with an average of up to 15 years after. [6] A preventative measure that can be utilized is prophylactic radiotherapy when a bilateral adrenalectomy is being performed in order to prevent Nelson's syndrome from manifesting. [7] Screening can also be done with the help of an MRI in order to visualize the pituitary for tumors. If tumors are not present then an MRI should be performed at intervals. [8] Hyper-pigmentation and fasting ACTH levels within plasma above 154 pmol/L are predictive of Nelson's syndrome after an adrenalectomy. [8] Risk factors include being younger in age and pregnancy. [2]

Mechanism

After a bilateral adrenalectomy is performed cortisol levels are no longer normal. This increases CRH production because it is not suppressed within the hypothalamus anymore. The increased CRH levels promote the growth of the tumor. Mutations with genes and with the glucocorticoid receptor can affect the tumor as well. Furthermore, differences between Nelson syndrome and Cushing's disease have been studied. Particularly Nelson's syndrome differs from Cushing's disease due to the following: secretions from the tumors, replacement of glucocorticoids, and injury to the hypothalamus due to radiation therapy utilized on the patient. [2] The pathophysiology of Nelson's syndrome is not understood very well. [6] Corticotrophinomas are generated from corticotroph cells. [6] Expression of functional CRH and vasopressin V3 receptors increase in number. [6] Additionally, there are two isoforms of glucocorticoid receptors. Heterozygosity loss in the glucocorticoid receptor can occur in the tumors present from Nelson's syndrome. [6] Overall, not all patients that have had a total bilateral adrenalectomy develop Nelson's syndrome, which makes the mechanism harder to understand for such a rare disease. [9] It is not clear whether the adrenalectomy or reduced cortisol secretion causes aggressive tumor growth. [10]

Diagnosis

Common diagnostic techniques include: [11]

Blood samples are assessed for the absence or presence of aldosterone and cortisol. [4] Physical examinations are also useful in patients in order to examine vision, skin pigmentation, how the body replaces steroids, and the cranial nerves. [5] Recent advancements in high-resolution MRIs allow for adenomas to be detected during the early stages of Nelson syndrome. [2] Physical examination including height, weight, vital signs, blood pressure, eye examination, thyroid examination, abdominal examination, neurological examination, skin examination and pubertal staging needs to be assessed. [5] Through blood pressure and pulse readings can indicate hypothyroidism and adrenal insufficiency. [5] Hyper-pigmentation, hyporeflexia, and loss of vision can also indicate Nelson's syndrome when assessed together. [5] Specifically for a child who might have Nelson's syndrome, the patient should be questioned about the symptoms of the disease, and well as symptoms of other diseases to narrow down which disease the patient presents with. The patient should be questioned about how often and to what degree headaches, visual disturbances, and symptoms associated with pituitary malfunction occur. Additionally, adrenal steroid replacement should be assessed.[ citation needed ]

Treatment

Common treatments for Nelson's syndrome include radiation or surgical procedure. Radiation allows for the limitation of the growth of the pituitary gland and the adenomas. If the adenomas start to affect the surrounding structures of the brain, then a micro-surgical technique can be adapted in order to remove the adenomas in a transsphenoidal (bone at base of the skull) process. [4] Death may result with development of a locally aggressive pituitary tumor. However, does not commonly occur with pituitary diseases. [10] In the rare case, ACTH-secreting tumors can become malignant. Morbidity from the disease can occur due to pituitary tissue compression or replacement, and compression of structures that surround the pituitary fossa. [2] The tumor can also compress the optic apparatus, disturb cerebrospinal fluid flow, meningitis, and testicular enlargement in rare cases. [2]

Research

Through multiple advancements within the medical field, caregivers have been able to stray away from utilizing bilateral adrenalectomy as the treatment for Cushing's disease. This has decreased the risk of patients presenting with Nelson's syndrome. Alternative treatments for Nelson's syndrome have been discovered. The most utilized technique for Nelson's syndrome has been transsphenoidal surgery. In addition, pharmacotherapy, radiotherapy, and radiosurgery have been utilized accompanying a surgical procedure. Pharmacological drugs can also be given accompanying a transsphenoidal surgery including the following: pasireotide, temozolomide and octreotide. [7] Within rats/mice, rosiglitazone has been an effective measure, however this has not been discovered in humans yet. [7]

Related Research Articles

<span class="mw-page-title-main">Adrenal gland</span> Endocrine gland

The adrenal glands are endocrine glands that produce a variety of hormones including adrenaline and the steroids aldosterone and cortisol. They are found above the kidneys. Each gland has an outer cortex which produces steroid hormones and an inner medulla. The adrenal cortex itself is divided into three main zones: the zona glomerulosa, the zona fasciculata and the zona reticularis.

<span class="mw-page-title-main">Adrenocorticotropic hormone</span> Pituitary hormone

Adrenocorticotropic hormone is a polypeptide tropic hormone produced by and secreted by the anterior pituitary gland. It is also used as a medication and diagnostic agent. ACTH is an important component of the hypothalamic-pituitary-adrenal axis and is often produced in response to biological stress. Its principal effects are increased production and release of cortisol by the cortex of the adrenal gland. ACTH is also related to the circadian rhythm in many organisms.

<span class="mw-page-title-main">Cushing's syndrome</span> Symptoms from excessive exposure to glucocorticoids such as cortisol

Cushing's syndrome is a collection of signs and symptoms due to prolonged exposure to glucocorticoids such as cortisol. Signs and symptoms may include high blood pressure, abdominal obesity but with thin arms and legs, reddish stretch marks, a round red face, a fat lump between the shoulders, weak muscles, weak bones, acne, and fragile skin that heals poorly. Women may have more hair and irregular menstruation. Occasionally there may be changes in mood, headaches, and a chronic feeling of tiredness.

<span class="mw-page-title-main">Anterior pituitary</span> Anterior lobe of the pituitary gland

A major organ of the endocrine system, the anterior pituitary is the glandular, anterior lobe that together with the posterior lobe makes up the pituitary gland (hypophysis). The anterior pituitary regulates several physiological processes, including stress, growth, reproduction, and lactation. Proper functioning of the anterior pituitary and of the organs it regulates can often be ascertained via blood tests that measure hormone levels.

<span class="mw-page-title-main">Cortisol</span> Human natural glucocorticoid hormone

Cortisol is a steroid hormone, in the glucocorticoid class of hormones. When used as a medication, it is known as hydrocortisone.

Cushing's disease is one cause of Cushing's syndrome characterised by increased secretion of adrenocorticotropic hormone (ACTH) from the anterior pituitary. This is most often as a result of a pituitary adenoma or due to excess production of hypothalamus CRH that stimulates the synthesis of cortisol by the adrenal glands. Pituitary adenomas are responsible for 80% of endogenous Cushing's syndrome, when excluding Cushing's syndrome from exogenously administered corticosteroids. The equine version of this disease is Pituitary pars intermedia dysfunction.

<span class="mw-page-title-main">Adrenal insufficiency</span> Medical condition

Adrenal insufficiency is a condition in which the adrenal glands do not produce adequate amounts of steroid hormones, primarily cortisol; but may also include impaired production of aldosterone, which regulates sodium conservation, potassium secretion, and water retention. Craving for salt or salty foods due to the urinary losses of sodium is common.

Corticotropes are basophilic cells in the anterior pituitary that produce pro-opiomelanocortin (POMC) which undergoes cleavage to adrenocorticotropin (ACTH), β-lipotropin (β-LPH), and melanocyte-stimulating hormone (MSH). These cells are stimulated by corticotropin releasing hormone (CRH) and make up 15–20% of the cells in the anterior pituitary. The release of ACTH from the corticotropic cells is controlled by CRH, which is formed in the cell bodies of parvocellular neurosecretory cells within the paraventricular nucleus of the hypothalamus and passes to the corticotropes in the anterior pituitary via the hypophyseal portal system. Adrenocorticotropin hormone stimulates the adrenal cortex to release glucocorticoids and plays an important role in the stress response.

<span class="mw-page-title-main">Metyrapone</span> Chemical compound

Metyrapone, sold under the brand name Metopirone, is a medication which is used in the diagnosis of adrenal insufficiency and occasionally in the treatment of Cushing's syndrome (hypercortisolism).

Sheehan's syndrome, also known as postpartum pituitary gland necrosis, is hypopituitarism, caused by ischemic necrosis due to blood loss and hypovolemic shock during and after childbirth.

<span class="mw-page-title-main">Pituitary adenoma</span> Human disease

Pituitary adenomas are benign tumors that occur in the pituitary gland. Most pituitary tumors are benign, approximately 35% are invasive and just 0.1% to 0.2% are carcinomas. Pituitary adenomas represent from 10% to 25% of all intracranial neoplasms and the estimated prevalence rate in the general population is approximately 17%.

<span class="mw-page-title-main">Adrenocortical carcinoma</span> Medical condition

Adrenocortical carcinoma (ACC) is an aggressive cancer originating in the cortex of the adrenal gland.

<span class="mw-page-title-main">Dexamethasone suppression test</span> Medical test

The dexamethasone suppression test (DST) is used to assess adrenal gland function by measuring how cortisol levels change in response to oral doses or an injection of dexamethasone. It is typically used to diagnose Cushing's syndrome.

<span class="mw-page-title-main">Hyperpituitarism</span> Medical condition

Hyperpituitarism is a condition due to the primary hypersecretion of pituitary hormones; it typically results from a pituitary adenoma. In children with hyperpituitarism, disruption of growth regulation is rare, either because of hormone hypersecretion or because of manifestations caused by local compression of the adenoma.

In humans and other animals, the adrenocortical hormones are hormones produced by the adrenal cortex, the outer region of the adrenal gland. These polycyclic steroid hormones have a variety of roles that are crucial for the body’s response to stress, and they also regulate other functions in the body. Threats to homeostasis, such as injury, chemical imbalances, infection, or psychological stress, can initiate a stress response. Examples of adrenocortical hormones that are involved in the stress response are aldosterone and cortisol. These hormones also function in regulating the conservation of water by the kidneys and glucose metabolism, respectively.

Pituitary apoplexy is bleeding into or impaired blood supply of the pituitary gland. This usually occurs in the presence of a tumor of the pituitary, although in 80% of cases this has not been diagnosed previously. The most common initial symptom is a sudden headache, often associated with a rapidly worsening visual field defect or double vision caused by compression of nerves surrounding the gland. This is often followed by acute symptoms caused by lack of secretion of essential hormones, predominantly adrenal insufficiency.

Hypophysectomy is the surgical removal of the hypophysis. It is most commonly performed to treat tumors, especially craniopharyngioma tumors. Sometimes it is used to treat Cushing's syndrome due to pituitary adenoma or Simmond's disease It is also applied in neurosciences to understand the functioning of hypophysis. There are various ways a hypophysectomy can be carried out. These methods include transsphenoidal hypophysectomy, open craniotomy, and stereotactic radiosurgery.

<span class="mw-page-title-main">Adrenocortical adenoma</span> Medical condition

Adrenocortical adenoma is commonly described as a benign neoplasm emerging from the cells that comprise the adrenal cortex. Like most adenomas, the adrenocortical adenoma is considered a benign tumor since the majority of them are non-functioning and asymptomatic. Adrenocortical adenomas are classified as ACTH-independent disorders, and are commonly associated with conditions linked to hyperadrenalism such as Cushing's syndrome (hypercortisolism) or Conn's syndrome (hyperaldosteronism), which is also known as primary aldosteronism. In addition, recent case reports further support the affiliation of adrenocortical adenomas with hyperandrogenism or florid hyperandrogenism which can cause hyperandrogenic hirsutism in females. "Cushing's syndrome" differs from the "Cushing's disease" even though both conditions are induced by hypercortisolism. The term "Cushing's disease" refers specifically to "secondary hypercortisolism" classified as "ACTH-dependent Cushing's syndrome" caused by pituitary adenomas. In contrast, "Cushing's syndrome" refers specifically to "primary hypercortisolism" classified as "ACTH-independent Cushing's syndrome" caused by adrenal adenomas.

Inferior petrosal sinus sampling, is a diagnostic medical procedure used to determine whether excess adrenocorticotropic hormone (ACTH) is coming from the pituitary gland or from a source outside the pituitary. The procedure is usually reserved for patients with consistent ACTH-dependent Cushing's syndrome without a clear cut lesion on pituitary MRI.

<span class="mw-page-title-main">Primary pigmented nodular adrenocortical disease</span> Medical condition

Primary pigmented nodular adrenocortical disease (PPNAD) was first coined in 1984 by Carney et al. it often occurs in association with Carney complex (CNC). CNC is a rare syndrome that involves the formation of abnormal tumours that cause endocrine hyperactivity.

References

  1. ↑ Papakokkinou, Eleni; Piasecka, Marta; Carlsen, Hanne Krage; Chantzichristos, Dimitrios; Olsson, Daniel S.; Dahlqvist, Per; Petersson, Maria; Berinder, Katarina; Bensing, Sophie; Höybye, Charlotte; Engström, Britt Edén; Burman, Pia; Follin, Cecilia; Petranek, David; Erfurth, Eva Marie; Wahlberg, Jeanette; Ekman, Bertil; Åkerman, Anna-Karin; Schwarcz, Erik; Johannsson, Gudmundur; Falhammar, Henrik; Ragnarsson, Oskar (October 2021). "Prevalence of Nelson's syndrome after bilateral adrenalectomy in patients with cushing's disease: a systematic review and meta-analysis". Pituitary. 24 (5): 797–809. doi:10.1007/s11102-021-01158-z. PMID   34036460 . Retrieved 10 August 2022.
  2. 1 2 3 4 5 6 7 8 9 "Nelson Syndrome: Background, Pathophysiology, Epidemiology". 2017-05-03.{{cite journal}}: Cite journal requires |journal= (help)
  3. ↑ "the definition of nelson syndrome". Dictionary.com. Retrieved 2015-11-05.
  4. 1 2 3 "Nelson Syndrome - NORD (National Organization for Rare Disorders)". NORD (National Organization for Rare Disorders). Retrieved 2015-11-05.
  5. 1 2 3 4 5 "Nelson Syndrome Clinical Presentation: History, Physical, Causes". emedicine.medscape.com. Retrieved 2015-11-05.
  6. 1 2 3 4 5 Barber, T. M.; Adams, E.; Ansorge, O.; Byrne, J. V.; Karavitaki, N.; Wass, J. a. H. (2010-10-01). "Nelson's syndrome". European Journal of Endocrinology. 163 (4): 495–507. doi: 10.1530/EJE-10-0466 . ISSN   0804-4643. PMID   20668020.
  7. 1 2 3 Patel, Jimmy; Eloy, Jean Anderson; Liu, James K. (2015-02-01). "Nelson's syndrome: a review of the clinical manifestations, pathophysiology, and treatment strategies". Neurosurgical Focus. 38 (2): E14. doi: 10.3171/2014.10.FOCUS14681 . PMID   25639316.
  8. 1 2 Pereira, Maria A. Albergaria; Halpern, Alfredo; Salgado, Luiz Roberto; Mendonça, Berenice B.; Nery, Marcia; Liberman, Bernardo; Streeten, David H. P.; Wajchenberg, Bernardo L. (1998-10-01). "A study of patients with Nelson's syndrome". Clinical Endocrinology. 49 (4): 533–539. doi:10.1046/j.1365-2265.1998.00578.x. ISSN   1365-2265. PMID   9876353. S2CID   21323528.
  9. ↑ "Nelson's Syndrome. Read about Nelson's syndrome | Patient". Patient. Retrieved 2015-12-10.
  10. 1 2 Munir, Alia; Newell-Price, John (2007). "Nelson's Syndrome". Arquivos Brasileiros de Endocrinologia & Metabologia. 51 (8): 1392–1396. doi: 10.1590/S0004-27302007000800026 . ISSN   0004-2730. PMID   18209878.
  11. ↑ Monserrate A, De Jesus O. "Nelson Syndrome". National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 11 July 2021.
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