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What Are the Parathyroid Glands?

Peppered throughout the human body are small organs known as glands. These organs have a complex and important job without which we couldn’t survive. They produce hormones that keep the body functioning properly.

Among the most critical are the endocrine glands. These include the pituitary gland, which secretes hormones regulating growth, pain relief and sex function, among others, and the adrenal glands, which produce stress hormones. Another key member of this group is the thyroid gland, which regulates the body’s use of energy, creation of proteins and sensitivity to other hormones.

About the Parathyroid Glands

The parathyroid glands are attached to the thyroid, but despite the similar names, they play a different role. The parathyroids are usually located on the back surface of the thyroid, in the portion of the neck between the Adam’s apple and the collarbone. There are typically four of them.

These small glands release a substance known as parathyroid hormone, or PTH. Its primary purpose is to regulate the body’s blood calcium levels, a task it shares with the thyroid. It also has an effect on the body’s absorption of phosphate. See the picture below for thyroid and parathyroid gland anatomy.

The thyroid gland produces a hormone called calcitonin that limits the level of calcium in the blood. PTH works as an antagonist to this hormone and together they keep calcium levels within a very narrow range. PTH also increases phosphate absorption by activating vitamin D in the kidney.

The parathyroid glands, like the thyroid, come with their own set of disorders. Overproduction of hormones by the thyroid can lead to the well-known conditions hypothyroidism and hyperthyroidism. Less well-known are the conditions hypoparathyroidism and hyperparathyroidism.

Underactive Parathyroid

Hypoparathyroidism occurs when the parathyroids produce too little PTH. This results in low blood calcium levels, which in turn results in symptoms including cramping, involuntary muscle spasms and unpleasant tingling. Headaches, insomnia, abdominal pain, fatigue and bone pain are also possible.

Hypoparathyroidism is a serious condition and it can cause medical emergencies, including seizures, irregular heartbeats and respiratory failure. There are a number of possible causes, such as removal of the parathyroid glands during surgery, autoimmune disorders, hemochromatosis and magnesium deficiency, among others. It can also be inherited.

Overactive Parathyroid

Hyperparathyroidism, meanwhile, results from an overproduction of PTH. Primary hyperparathyroidism occurs when the glands actually malfunction. This can be caused by hyperplasia (increased cell production), adenoma (a benign tumour) or, in extremely rare cases, carcinoma (cancer) of the parathyroids. Patients with bipolar disorder who take lithium long-term are also at greater risk for primary hyperparathyroidism, since that drug can lower calcium levels, leading to stimulated production of PTH.

Secondary hyperparathyroidism is caused by any medical condition that leads to lowered calcium levels in the blood. Chronic kidney failure and vitamin D deficiency are the most common factors leading to this disorder.

About half of all patients with hyperparathyroidism are identified by medical tests before they show any signs. Low calcium rarely causes overt distress though depression, bone pain, osteoporosis, nausea, decreased appetite and kidney stones are among the possible symptoms. Bone loss is possible.

If you have questions or concerns about thyroid problems see your local doctor who will arrange for you to see a thyroid surgeon.  

 

For more information about the parathyroid glands click here.

The post What Are the Parathyroid Glands? appeared first on Thyroid Clinic Sydney.

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By Ashleigh Elkins

This article discusses the management of patients who have atypical thyroid nodules. Thyroid nodules are quite common in the general population. Thyroid nodules may be detected because some people feel a lump in their neck or throat, whilst in other people there are no symptoms and the nodule is found incidentally on ultrasound examination.

Thyroid nodules are usually investigated with a fine needle aspiration (FNA) of cells from the nodule, to determine whether the nodule is benign or malignant, and therefore to guide patient management.

Bethesda Classification System

Thyroid FNA results obtained from patients with thyroid nodules are usually reported according to the Bethesda classification system. This system is made up of six categories which correlate to an estimated risk of malignancy. The Bethesda system is used to help guide the appropriate management of the patient with a thyroid nodule.(1)

The Bethesda classification is summarised in the following table.

Diagnostic Category Diagnostic category name Risk of malignancy Typical management
I Non-diagnostic or unsatisfactory 1-4% Repeat FNA under ultrasound guidance
II Benign 0-3% Clinical follow-up
III Atypia of undetermined significance or follicular lesion of undetermined significance 5-15% Repeat FNA, further investigation
IV Follicular neoplasm or suspicious for follicular neoplasm 15-30% Surgical lobectomy
V Suspicious for malignancy 60-75% Near-total thyroidectomy or surgical lobectomy
VI Malignant 97-99% Near-total thyroidectomy

Table 1: Overview of the Bethesda classification, associated risk of malignancy and typical management of patients.(1)

Bethesda Classification Category III

The results of FNA cytology that fall into the Bethesda category III do not easily fit within the benign, malignant or suspicious for malignancy categories. Bethesda category III is the least common result obtained from FNA of a thyroid nodule.(2)

There are many different findings which can be classified within the Bethesda category III. Some of these scenarios include:

  1. The cells obtained from the FNA are made up primarily of microfollicles, but the sample does not meet the criteria for category IV; follicular neoplasm/suspicious for follicular neoplasm
  2. Sample consists mainly of Hurthle cells and scant colloid
  3. The cellular atypia are difficult to interpret due to artifacts which have occurred during the preparation of the slide for analysis; such as clotting or air-drying.
  4. Sample predominantly made up of Hurthle cells, and clinical features suggest a benign nodule, such as in patients with Hashimoto’s thyroiditis or multinodular goitre
  5. Some features suggestive of papillary thyroid carcinoma, but overall, the sample appears benign. This is usually seen in samples obtained from patients with Hashimoto’s thyroiditis
  6. Some cells lining a cyst have some features which look atypical, but the remainder of the sample is largely benign
  7. A small number of follicular cells display nuclear enlargement and/or prominent nucleoli. This pattern is typically seen in patients who have undergone radioactive iodine treatment, or those with cystic degeneration/haemorrhage
  8. Atypical lymphoid infiltrate, but the degree of atypia is not sufficient to be classified as suspicious for malignancy.(2)

Management of patients who have atypical thyroid nodules

Because many different results are placed into Bethesda category III, the clinical management of patients with these nodules is varied, and there is no consensus as to the best approach to management.(3) Patients may undergo a repeat FNA assessment, generally three months after the initial FNA. In the majority of cases, a repeat FNA will return a more definitive result. However, in approximately 20% of cases, repeat FNA will also return a result of Bethesda category III.(2) Other potential management strategies include observation, further investigation, such as with ultrasound and in some cases, referral for surgery.

Ultrasound can be used to guide FNA to ensure the sampled cells are taken from the nodule. It can also be used to evaluate the characteristics of the nodule, including echogenicity, irregular margins, presence of microcalcifications and vascularity.(3) These sonographic features have been associated with an increased risk of malignancy in Bethesda III nodules.(4) Norlen et al (3) found that if ultrasound in patients with Bethesda III nodules did not show any hypoechogenicity, irregular margins or microcalcifications, the risk of the patient having a malignant nodule was very low. Hence, ultrasound assessment of the nodule may help to guide the patient’s management.

The management of Bethesda category III nodules is dependent on patient and clinical factors. Patients who are thought to be at a low risk of malignancy may be observed clinically for a period of time, or have a repeat FNA assessment three months later. Patients who have an FNA result revealing a Bethesda category III nodule who are thought to be at a high risk of malignancy may be referred directly for surgery without a repeat FNA. These patients are typically young, and have sonographic or clinical features which are concerning for malignancy. Male patients are also more likely to be referred for surgery directly than female patients.(5)

When to operate and which operation?

The surgical management of an atypical thyroid nodule depends upon patient and clinical factors. Nodulectomy is not routinely performed in the setting of atypical thyroid nodules. This is a procedure which removes the nodule and a small section of surrounding tissue. When malignancy is suspected, this procedure is not recommended for several reasons. Firstly, only a small amount of tissue is resected and this may not be sufficient to remove all potentially malignant cells. Secondly, there is also the potential to spread potentially cancerous cells into other compartments of the neck during nodulectomy. Finally, the risk of post-operative bleeding complications is significantly higher following nodulectomy.

The size of the nodule is often used to determine whether a hemithyroidectomy or total thyroidectomy is performed. For nodules which are smaller than 1cm in diameter and are suspicious for malignancy, a hemithyroidectomy is usually performed.(6) However, a limitation of performing a hemithyroidectomy is that patients may later develop disease in the remaining thyroid lobe and hence may require completion thyroidectomy at a later stage.

For nodules greater than 1cm in diameter which are suspicious for malignancy, a total thyroidectomy is usually the preferred surgical procedure. Other indications for total thyroidectomy include pathology in both lobes of the thyroid gland, and if there is suspicion of metastatic spread to the lymph nodes of the neck.(6) Patients who are found to have papillary thyroid cancer will usually undergo total thyroidectomy, and may also require a central lymph node dissection. This is because there are high rates of metastatic disease to the lymph nodes with papillary thyroid cancer, estimated to be found in approximately 20-50% of patients. In order to reduce the risk of recurrence, a central lymph node clearance is often performed in patients with known papillary thyroid cancer.(7)

References

[1] Bongiovanni M, Spitale A, Faquin WC, Mazzucchelli L, Baloch ZW. The Bethesda system for reporting thyroid cytopathology: A meta-analysis. Acta Cytologica 2012;56:333–339.

[2] Cibas ES, Ali SZ. The Bethesda system for reporting thyroid cytopathology. Am J Clin Pathol 2009;132:658-665.

[3] Norlen O, Popadich A, Kruijff S, Gill AJ, Sarkis LM, Delbridge L, Sywak M, Sidhu S. Bethesda III thyroid nodules: The role of ultrasound in clinical decision making. Ann Surg Oncol (2014) 21:3528–3533.

[4] Gweon HM, Son EJ, Youk JH, Kim JA. Thyroid nodules with Bethesda system III cytology: Can ultrasonography guide the next step? Ann Surg Oncol (2013) 20:3083–3088.

[5] Nagarkatti SS, Faquin WC, Lubitz CC, Garcia DM, Barbesino G, Ross DS, Hodin RA, Daniels GH, Parangi S. The management of thyroid nodules with atypical cytology on fine needle aspiration biopsy. Ann Surg Oncol. 2013 January ; 20(1):

[6] Chung YS, Yoo C, Jung JH, Choi HJ, Suh YJ. Review of atypical cytology of thyroid nodule according to the Bethesda system and its beneficial effect in the surgical treatment of papillary carcinoma. J Korean Surg Soc. 2011 Aug; 81(2): 75–84.

[7] Calo PG, Pisano G, Medas F, Marcialis J, Gordini L, Erdas E, Nicolosi A. Total thyroidectomy without prophylactic central neck dissection in clinically node-negative papillary thyroid cancer: is it an adequate treatment? World Journal of Surgical Oncology 2014, 12:152

The post Management of Atypical Thyroid Nodules appeared first on Thyroid Clinic Sydney.

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The thyroid gland affects many body systems and physiological processes, including fertility and reproduction. Disorders of the thyroid gland, such as hypothyroidism and hyperthyroidism, can affect fertility, miscarriage and pregnancy outcomes.

Subfertility is a term used to describe a state of reduced fertility; where it takes a longer time than expected to conceive. Subfertility affects around 1-5% of couples globally. Associations have been drawn between thyroid disorders and subfertility. Hyperthyroidism has an incidence of 1.5% amongst women in the general population; however, this rate may be as high as 2.3% in women affected by subfertility. Hyperthyroidism can cause problems with the menstrual cycle, such as menstrual irregularity and heavy bleeding. Despite the effect of hyperthyroidism on fertility, there is little evidence to suggest that treatments for hyperthyroidism improve ovulation.

Hypothyroidism can also affect fertility.  This is related to the hormonal control of ovulation. In hypothyroidism, the release of a hormone from the hypothalamus called gonadotrophin releasing hormone (GnRH). This hormone is usually released in bursts. When released in bursts, the GnRH stimulates the release of two hormones from the pituitary gland called follicle-stimulating hormone and luteinising hormone, which help to control ovulation. In hypothyroidism, GnRH is not released in bursts, which can affect the process of ovulation. Additionally, hypothyroid patients have high levels of thyroid stimulating hormone (TSH). High levels of TSH have been associated with disturbances to the menstrual cycle and an increase in the number of menstrual cycles in which ovulation does not occur (anovulatory cycles). There are higher rates of hypothyroidism amongst subfertile women, and also women who present with subfertility tend to have higher blood levels of TSH. Treatment with thyroxine can improve fertility in hypothyroid women.

Several autoimmune diseases have been associated with subfertility, including type 1 diabetes and lupus. Autoimmune thyroid disease and thyroid autoantibodies may also be associated with subfertility, as there is a higher prevalence of thyroid autoantibodies amongst subfertile patients than in the wider community.

Reference

Jefferys A, Vanderpump M, Yasmin E. Thyroid dysfunction and reproductive health. The Obstetrician & Gynaecologist, 2015, 17:39-45. http://onlinelibrary.wiley.com

 

The post Thyroid Problems and Fertility appeared first on Thyroid Clinic Sydney.

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By Ashleigh Elkins

The parathyroid glands are four small, pea-sized glands that are located behind the larger, butterfly-shaped thyroid gland. The parathyroid glands are named for their location. There are two superior thyroid glands, which are found behind the top part of the thyroid lobes; one behind the right thyroid lobe and one behind the left thyroid lobe. There are also two inferior parathyroid glands which can vary in their location. They are usually found behind the lower part of the right and left thyroid lobes. In some people, the inferior parathyroid glands may be located below the level of the thyroid gland, or may be found near the inferior thyroid veins. The parathyroid glands are usually 6mm in length and 3-4mm wide.

The parathyroid glands are involved in the regulation of blood calcium levels. This is important to ensure normal function of other organs and tissues, including the heart, kidneys, bones and nerves. The parathyroid glands produce a hormone called parathyroid hormone, or PTH, which controls the levels of calcium in the body. When the level of calcium in the blood drops, the parathyroid glands release PTH which works in a number of ways to increase the level of calcium in the blood.

Parathyroid hormone functions

rci.rutgers.edu

Parathyroid hormone – PTH

  • PTH acts on the bone to stimulate reabsorption of bone which results in the release of calcium stored in the bone
  • PTH acts on the kidney to increase the amount of calcium that is reabsorbed so that less calcium is lost through the urine
  • PTH also stimulates the activation of vitamin D in the kidney. Activated vitamin D is important because it helps the small intestine to reabsorb more calcium from the diet into the bloodstream

All of these actions work to increase the level of calcium. Once the calcium levels have returned to normal or become too high, the parathyroid glands become less active and do not secrete as much PTH.

Relationship between blood ionized calcium concentrations and plasma parathyroid hormone (PTH) levels in persons with normal renal and parathyroid gland function. American Journal of Physiology – Renal Physiology Published 6 May 2004 Vol. 286 no. 6.

What is hyperparathyroidism?

Hyperparathyroidism is a term used to describe increased activity in one or more of the parathyroid glands. There are three types of hyperparathyroidism:

Primary hyperparathyroidism, where the affected parathyroid gland produces too much PTH as a result of a problem within the parathyroid gland itself. The most common cause of primary hyperparathyroidism is a benign tumour within the gland called a parathyroid adenoma. Parathyroid adenomas are usually only found within one parathyroid gland, it is very uncommon to find a parathyroid adenoma in more than one gland. Less common causes of primary hyperparathyroidism include parathyroid hyperplasia, and very rarely, parathyroid carcinoma, a malignant parathyroid tumour.

Secondary hyperparathyroidism, where the underlying cause of the hyperparathyroidism is due to low levels of blood calcium, which is known as hypocalcaemia. Hypocalcaemia may be the result of poor calcium absorption in the intestines, or the result of severe dietary deficiency. Because vitamin D is necessary for calcium absorption, severe vitamin D deficiency can also cause hypocalcaemia and secondary hyperparathyroidism. People with chronic renal failure may also develop secondary hyperparathyroidism.

Tertiary hyperparathyroidism, which occurs after chronic secondary hyperparathyroidism. Once the underlying cause of the longstanding secondary hyperparathyroidism is addressed, the affected parathyroid gland or glands still continue to secrete too much PTH.

Parathyroid hormone testing

Parathyroid hormone levels are routinely measured by a blood test. Intact PTH (iPTH) is the biologically active form and is secreted when the calcium level is low. iPTH is the most frequently ordered parathyroid hormone test. iPTH is used to diagnose the cause of a high calcium level and to distinguish between parathyroid and non-parathyroid causes. A calcium test is almost always ordered along with an iPTH test. The key to diagnosis of a parathyroid gland disorder is the relationship between the calcium and iPTH and the response of the parathyroid glands to changing levels of calcium.

Symptoms

Symptoms of hyperparathyroidism can vary depending on whether the cause is primary, secondary or tertiary hyperparathyroidism. The symptoms of primary and tertiary hyperparathyroidism are similar, because both cause a high level of calcium in the bloodstream.

Symptoms of primary and tertiary hyperparathyroidism include:

  • Bone and joint pain due to the breakdown of bone to release calcium
  • Kidney stones
  • Frequent urination
  • Excessive thirst
  • Loss of appetite
  • Nausea
  • Constipation
  • Fractures
  • Gout

The symptoms of secondary hyperparathyroidism are different to the symptoms of primary and tertiary hyperparathyroidism because elevated levels of blood calcium cause many of the symptoms in primary and tertiary hyperparathyroidism; but high levels of blood calcium are not an issue with secondary hyperparathyroidism. Increased fracture risk is common to all forms of hyperparathyroidism. Underlying renal problems are the cause of many of the symptoms of secondary hyperparathyroidism.

Symptoms of secondary hyperparathyroidism include:

  • Fractures
  • Bone deformities
  • Changes to urinary habits
  • Ankle and leg swelling
  • Fatigue
  • Nausea
  • Vomiting
  • Itching

Treatment

Surgery is the most common treatment for primary hyperparathyroidism and provides a cure in about 95 percent of all cases. Your surgeon will remove only those glands that are enlarged or have a tumour (adenoma).

If all four glands are affected, your surgeon will likely remove only three glands and perhaps a portion of the fourth. This approach will leave some functioning parathyroid tissue.

Parathyroid surgery can be done through a very small neck incision which leaves a minimal scar.

Complications from parathyroid surgery are uncommon. Risks include damage to nerves controlling the vocal cords and long-term low calcium levels requiring the use of calcium and vitamin D supplements.

For more information about the parathyroid glands click here.

If you have questions about the parathyroid glands, contact your local doctor who will arrange for you to see a thyroid surgeon.

The post Symptoms of Hyperparathyroidism appeared first on Thyroid Clinic Sydney.

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Increased Thyroid Cancer Incidence

The incidence (i.e. the number of new cases) of thyroid cancer has seen an increase in the past few decades. However, during the same period of time, there has also been an increase in the utilisation of imaging and biopsy to help detect thyroid cancer. As a result, the increased incidence of thyroid cancer in the recent past may not actually be due to a true increase in the number of cases of thyroid cancer. Rather, that more cases of thyroid cancer are being detected with the increased use of ultrasound and fine needle aspiration.

Increased Use of Thyroid Ultrasound and Fine Needle Aspiration Biopsy

The study by Zevallos et al., aimed to determine if the increased thyroid cancer incidence observed corresponded with a similar increase in the use of diagnostic investigations. Thyroid ultrasound and fine needle aspiration. This was achieved by examining the Veteran’s Affairs health system records. The number of cases of thyroid cancer and the numbers of diagnostic investigations performed in the period between the years 2000 and 2012 were compared. At the commencement of the study in 2000, the incidence of thyroid cancer was 10.3 cases per 100,000 people. In comparison, at the study’s conclusion in 2012, the incidence of thyroid cancer was 21.5 cases per 100,000 people.

As with the incidence of thyroid cancer during the study period, the use of ultrasound and fine needle aspiration biopsy also exhibited an increase. In 2000, the rate of thyroid ultrasound was 125.6 per 100,000 people, which had increased to 572.1 per 100,000 people in 2012. Similarly, in 2000 the rate of fine needle aspiration biopsy was 7 per 100,000 people, but rose to 46.2 per 100,000 by 2012.

What this result really means is that due to better access to testing for thyroid cancer, the number of cases that are detected increases. This does not necessarily mean that thyroid cancer is becoming more common. Rather, we are becoming better at detecting it. This finding is also likely to be because patients with small thyroid nodules are being over-investigated. The American Thyroid Association (ATA) recommends that all patients with a thyroid nodule should have their thyroid stimulating hormone level tested. If this comes back with a low result, they recommend that the patient has a radionuclide thyroid scan. Additionally, the ATA also recommends that all patients with suspected or known thyroid nodules have an ultrasound assessment of the thyroid, and endorse that fine needle aspiration is the investigation of choice for a thyroid nodule.

References

Zevallos JP., et al. (2015). Increased thyroid cancer incidence corresponds to increased use of thyroid ultrasound and fine-needle aspiration: A study of the Veterans Affairs health care system. Cancer, 121(5), 741-746. http://www.ncbi.nlm.nih.gov/pubmed/25376872

Cooper DS, et al. (2009). Revised American Thyroid Association Management Guidelines for Patients with Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid, 19(11), 1167-1214. http://online.liebertpub.com/doi/full/10.1089/thy.2009.0110

The post Increased Thyroid Cancer Incidence & Increased Use of Thyroid Ultrasound and Fine Needle Aspiration Biopsy appeared first on Thyroid Clinic Sydney.

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