Approach to Parathyroid Disease 
Richard Davis, Naira Baregamian, Courtney Gibson 
 
OPEN MANUAL OF SURGERY IN RESOURCE-LIMITED SETTINGS 
www.vumc.org/global-surgical-atlas 
This work is licensed under a Creative Commons Attribution-ShareAlike 3.0 Unported License  
 
Background:  
 
The parathyroid diseases are unique in 
several 
ways. 
They 
have 
subtle 
clinical 
characteristics that can be ignored, overlooked, or 
blamed on other clinical entities. They are usually 
curable if treated well (except for parathyroid cancer, 
which has a very poor prognosis.) And they are 
usually best treated by surgery. This is especially true 
in 
resource-limited 
settings. 
In 
resource-rich 
countries, 
less-severe 
cases 
of 
secondary 
hyperparathyroidism 
can 
be 
treated 
with 
medications. But the mainstay of parathyroid disease 
treatment remains surgery.  
 
The cause of all of hyperparathyroidism’s 
symptoms is the inappropriate mobilization and 
elevation 
of 
calcium, 
stimulated 
by 
an 
inappropriately high level of serum parathyroid 
hormone (PTH.) This has several predictable effects, 
as described further below.  
 
In resource-rich countries, routine serum 
calcium assessment as part of a combined blood test 
panel (“Basic Metabolic Panel”) has led to an 
increase in diagnosis and treatment of Primary 
Hyperparathyroidism. In some cases, patients 
diagnosed in this way had symptoms such as mild 
abdominal pain or subclinical depression, that they 
didn’t even realize were problematic until after their 
hypercalcemia had been successfully treated.  
 
The 
usual 
clinical 
manifestations 
of 
hyperparathyroidism can be classified as follows: 
 
Kidney Stones:  
 
Elevated serum calcium leads to elevated 
levels of calcium in the urine, which leads to urinary 
tract calculus disease. Any patient presenting with an 
episode of urinary tract stones should be checked for 
serum hypercalcemia.  
 
Bone Pain and Bony Tumors: 
 
Parathyroid hormone stimulates the bone to 
release calcium. This leads to bone and joint pain and 
bone fragility. There is a characteristic x-ray finding 
of subperiosteal reabsorption which can best be seen 
on plain x-rays of the hand.  
 
Subperiosteal resorption can be a subtle finding. In the image 
on the left, there is some erosion of the outer cortex on the first 
phalanx of the index finger (Red arrow.) The cortex of the first 
and second phalanges is also “lacy” in appearance, rather 
than solid as seen in the normal x-ray on the right. The tufts of 
the distal phalanges on the left also contain much less bone 
(Blue arrow) than the normal distal phalanges on the right. 
Case courtesy of Dr. Tom Ellswood, from the case 
https://radiopaedia.org/cases/77849?lang=us (Left) and Dr. 
Dai Roberts, from the case 
https://radiopaedia.org/cases/80411?lang=us (Right.) 
 
 
Excessive forced bone release of calcium can 
also lead to bony tumors. These are called osteitis 
fibrosa cystica, or Brown tumors, and have a 
characteristic radiologic appearance. A patient’s 
initial presentation for hyperparathyroidism may be 
with a bony mass or a pathologic fracture of the 
tumor. These tumors resolve upon treatment of the 
hyperparathyroidism.  
 
Characteristic radiolucent appearance of osteitis fibrosa 
cystica, seen here in the radius. Case courtesy of Dr Hani 
Makky Al Salam, from the case 
https://radiopaedia.org/cases/12460?lang=us  
Approach to Parathyroid Disease 
Richard Davis, Naira Baregamian, Courtney Gibson 
 
OPEN MANUAL OF SURGERY IN RESOURCE-LIMITED SETTINGS 
www.vumc.org/global-surgical-atlas 
This work is licensed under a Creative Commons Attribution-ShareAlike 3.0 Unported License  
 
 
Abdominal Complaints 
 
Patients will complain of dull constant 
abdominal pain that is not relieved or exacerbated by 
any factors. Other gastrointestinal complaints can 
include constipation, gastric ulcers and worsening 
acid reflux. In our limited-resource setting, when 
patients present with chronic abdominal pain and no 
apparent diagnosis, a serum Calcium level is part of 
our workup (as described further below.)  
 
Neuropsychiatric Disturbances: 
Patients will complain of symptoms such as extreme 
fatigue, lack of concentration, short-term memory 
loss, anxiety, insomnia and amotivation. Sometimes 
these may be subclinical; the patient only realizes 
they were present after the hypercalcemia has 
resolved.  
 
Physiology and Anatomy 
 
Parathyroid hormone is released in response 
to hypocalcemia or hyperphosphatemia by the 
parathyroid glands, which are so named because they 
are located adjacent to the thyroid gland. The 
hormone’s effect is to cause absorption of calcium 
and phosphorus from the intestine and release of 
calcium by osteolysis from the bones. In the kidney, 
parathyroid hormone’s effect is to increase 
reabsorption of calcium and increase release of 
phosphorus.  
 
Schematic of the feedback loop of calcium and parathyroid 
hormone. Hypocalcemia directly stimulates parathyroid 
hormone release, which affects the bones, kidneys, and 
intestines. Source: Lofrese JJ, Basit H, Lappin SL. Physiology, 
Parathyroid. In: StatPearls [Internet]. Treasure Island (FL): 
StatPearls Publishing; 2022 Jan- 
 
 
Hyperparathyroidism is due to excessive 
parathyroid hormone secretion by one or more 
parathyroid glands, leading to hypercalcemia. 
Causes include primary, secondary, or tertiary 
hyperparathyroidism as well as parathyroid cancer, 
as explained further below.  
 
In patients presenting with hypercalcemia, 
secondary causes must be excluded, such as 
malignancy, multiple myeloma, parathyroid-related 
hormone related protein secreting tumors, Vitamin D 
deficiency, 
renal 
insufficiency, 
familial 
hypocalciuric 
hypercalcemia, 
granulomatous 
disease, use of thiazide diuretics or lithium, milk 
alkali syndrome, Paget’s disease, immobilization, 
and other endocrine disorders. 
 
Primary Hyperparathyroidism 
 
This disease is caused by one or more 
enlarged and independently functional, but not 
malignant parathyroid glands. In resource-rich 
settings, most patients are asymptomatic or with 
minimal 
symptoms. 
They 
present 
with 
hypercalcemia detected on routine blood work. They 
Approach to Parathyroid Disease 
Richard Davis, Naira Baregamian, Courtney Gibson 
 
OPEN MANUAL OF SURGERY IN RESOURCE-LIMITED SETTINGS 
www.vumc.org/global-surgical-atlas 
This work is licensed under a Creative Commons Attribution-ShareAlike 3.0 Unported License  
 
are then found to have an inappropriately elevated 
parathyroid hormone during further work up. Nearly 
15-20% 
of 
patients 
with 
primary 
hyperparathyroidism will present with multi-gland 
hyperplasia. Multi-gland hyperplasia will require 
subtotal parathyroidectomy (typically 3.5-gland 
resection), if indications for surgery have been met. 
 
Secondary Hyperparathyroidism 
 
This disease arises in patients with end-stage 
renal disease on dialysis, and results in global 
parathyroid hyperplasia and hyperfunction. Patients 
with this disease almost always present with normal 
or mildly elevated calcium with extremely high PTH 
levels. This PTH elevation is multifactorial. 
Persistent hyperphosphatemia due to renal failure is 
a stimulus for PTH secretion. Also, elevated 
phosphate levels complex with circulating calcium to 
make calcium phosphate, which deposits in the 
tissues and leads to lower calcium levels. Vitamin D 
deficiency also leads to increased PTH release. The 
end result of all of these processes is increased bone 
turnover, bone pain and fractures, increased 
calcification of all tissues (including coronary 
arteries,) and calcium phosphate deposits in soft 
tissues. Calciphylaxis, characteristic necrotic skin 
lesions caused by microvascular damage and 
calcium phosphate deposition, is another severe 
consequence of this process.  
Typically, medical management of secondary 
hyperparathyroidism is undertaken first with vitamin 
D supplementation, active vitamin D or its analogs 
and 
the 
calcimimetic 
medication 
cinacalcet. 
Parathyroidectomy 
is 
indicated 
if 
medical 
management fails. In resource-rich countries, the 
availability of cinacalcet has led to decreased need 
for parathyroidectomy in dialysis dependent patients. 
As resource-poor countries develop economically 
and dialysis becomes more common, it is reasonable 
to think that surgical treatment of this disease will 
become more common as well, especially in patients 
who cannot afford cinacalcet in the long term.  
 
Typical lesion of calciphylaxis in a fair-skinned person. In more 
extreme forms, these lesions may have a central eschar. They 
are very painful. Niels Olson, CC BY-SA 3.0 
 https://creativecommons.org/licenses/by-sa/3.0, 
via Wikimedia Commons 
 
Tertiary Hyperparathyroidism 
 
This disease occurs when an excess of PTH 
is secreted by parathyroid glands, usually after 
longstanding secondary hyperparathyroidism, that 
persists after successful renal transplantation. The 
typical patient has been on dialysis for years before 
the transplant. After normal renal function has been 
restored, the hypertrophied parathyroid tissue fails to 
resolve; instead it continues to secrete PTH, despite 
serum calcium levels that are within normal range or 
even elevated. Hypertrophied parathyroid glands 
also may become resistant to calcimimetic treatment. 
The 
primary 
treatment 
of 
tertiary 
hyperparathyroidism is surgery. The main indication 
for surgical treatment is persistent hypercalcemia 
and/or an increased PTH levels.  
 
Parathyroid Carcinoma 
 
Parathyroid carcinoma is one of the rarest 
human malignancies and presents with unequivocal 
biochemical diagnosis of hyperparathyroidism, 
dramatic elevation in parathyroid hormone and 
serum Calcium levels and altered mental status 
These patients need hospitalization for medical 
management of hypercalcemic crisis, followed by 
definitive surgical management of the tumor. 
Parathyroid carcinomas tend to be large, and may be 
locally invasive, requiring an en bloc resection of the 
mass. A dramatic presentation of hypercalcemia, 
such as a neck mass with very elevated calcium 
levels, should raise suspicion for this disease.  
Approach to Parathyroid Disease 
Richard Davis, Naira Baregamian, Courtney Gibson 
 
OPEN MANUAL OF SURGERY IN RESOURCE-LIMITED SETTINGS 
www.vumc.org/global-surgical-atlas 
This work is licensed under a Creative Commons Attribution-ShareAlike 3.0 Unported License  
 
 
Enlarged neck mass (Blue arrow) in a patient with parathyroid 
carcinoma. Source: http://www.endocrinesurgery.net.au, used 
with permission. 
 
Anatomic Considerations 
The parathyroid glands usually consist of two 
pairs, the upper and lower parathyroid glands, 
although up to six glands can exist. They normally 
reside adjacent to the thyroid gland, adherent or 
adjacent to its posterior surface. Both the superior 
and inferior parathyroid glands’ blood supply is from 
the inferior thyroid vessels.  
Normal parathyroid glands are 5-15mm in 
size, oval-shaped, and dark yellow or orange in color. 
They can be distinguished from surrounding fat by 
being darker in color than fat. They are usually found 
in the loose tissue that surrounds the capsule of the 
thyroid. Careful dissection of this capsule, removing 
the loose tissue from the thyroid without causing 
damage to this tissue, will usually help you preserve 
the parathyroid gland. When a parathyroid is 
identified during capsular dissection of the thyroid, 
be aware of its blood supply, which usually enters the 
gland from the dorsal and caudal side.  
 
Parathyroid tumor (right) within the resected thymus gland 
shows the difference in color between parathyroid and fatty 
tissue. Source: http://www.endocrinesurgery.net.au, used with 
permission. 
 
The normal location of the glands is highly 
related to the location of the recurrent laryngeal 
nerve. Another useful landmark for localizing the 
glands is the tubercle of Zuckerkandl, the posterior-
most projection of the thyroid gland. The superior 
parathyroid glands will almost always be posterior to 
a line drawn through the recurrent laryngeal nerve; 
the inferior glands will normally be anterior to this 
line. Parathyroid adenomas are frequently found 
adjacent or adherent to the recurrent laryngeal nerve, 
which must be meticulously preserved during 
dissection.  
 
The location of the parathyroid glands relative to landmarks 
seen during neck exploration. The horizontal line goes through 
the tubercle of Zuckerkandl, the most posterolateral part of the 
thyroid gland. The vertical line is an imaginary line drawn 
along the course of recurrent laryngeal nerve. Note that the 
superior parathyroid glands can be cranial to the entrance of 
the nerve into the larynx, even though this anatomic relation is 
preserved. 
Source: 
Source: 
http://www.endocrinesurgery.net.au, used with permission. 
 
 
When a thorough search fails to show four 
glands adjacent to the thyroid gland in the above-
described locations, you are dealing with one or more 
glands in an ectopic location. An understanding of 
the embryology of the parathyroid development is 
crucial in this situation. Parathyroid ectopic locations 
can range from high cervical position, inside the 
carotid 
sheath, 
intrathyroidal, 
within 
the 
tracheoesophageal 
groove, 
retroesophageal, 
mediastinal, or within the thymus gland in the chest. 
Identifying the parathyroid vascular stalk and where 
parathyroid blood supply is coming from in relation 
to the recurrent laryngeal nerve can be very helpful 
Approach to Parathyroid Disease 
Richard Davis, Naira Baregamian, Courtney Gibson 
 
OPEN MANUAL OF SURGERY IN RESOURCE-LIMITED SETTINGS 
www.vumc.org/global-surgical-atlas 
This work is licensed under a Creative Commons Attribution-ShareAlike 3.0 Unported License  
 
in identifying which gland, superior or inferior, is 
being resected. This dilemma is discussed further in 
the following chapters. 
 
The superior parathyroid glands arise from 
the 4th pharyngeal pouch in the embryonic 
oropharynx. They do not travel far from this position 
to their final location in the neck. If you are having 
trouble finding an upper parathyroid, continue 
searching in the area of the upper thyroid lobe, 
especially along the superior thyroid vessels above 
the upper pole, within the tracheoesophageal groove, 
or in the retroesophageal position.  
 
Conversely, the inferior parathyroid glands 
arise from the 3rd pharyngeal pouch and migrate 
farther before reaching their location in the neck. 
This process is more prone to disturbances in 
migration, leading to a more frequent ectopic 
location.  
 
Embryology of the pharynx, 6th to 7th week of development. 
The inferior parathyroids originate in the third branchial pouch 
and the superior parathyroids originate in the fourth branchial 
pouch. Both migrate downwards into the neck: as the inferior 
parathyroids have farther to travel, they are more prone to 
migrate to an ectopic location. Source: 
http://www.endocrinesurgery.net.au, used with permission.  
 
Potential ectopic locations of the parathyroid glands. See the 
text for details. Source: http://www.endocrinesurgery.net.au, 
used with permission. 
 
Therefore, the surgeon who is having trouble 
finding a lower parathyroid gland should expand the 
search to the following locations: retro-esophageal, 
within the carotid sheath, within the thymus gland in 
the upper mediastinum, and within the thyroid gland 
itself. More specific advice for dealing with ectopic 
parathyroid glands is given further below and in the 
individual chapters.  
 
 
Principles:  
 
Surgeons 
who 
do 
not 
have 
specific 
experience 
with 
parathyroid 
disease 
may 
nevertheless have considerable experience locating 
and preserving parathyroid glands from performing 
thyroid resections. As with thyroid surgery, the best 
results come from hands that are experienced 
operating in this area. Carful technique with 
meticulous attention to hemostasis is crucial: it is 
much harder to distinguish parathyroid tissue, and to 
tell it from the surrounding fat, in a blood-stained 
field.  
Approach to Parathyroid Disease 
Richard Davis, Naira Baregamian, Courtney Gibson 
 
OPEN MANUAL OF SURGERY IN RESOURCE-LIMITED SETTINGS 
www.vumc.org/global-surgical-atlas 
This work is licensed under a Creative Commons Attribution-ShareAlike 3.0 Unported License  
 
 
The 
minimally 
invasive 
single-gland 
parathyroidectomy described in this Manual should 
be used when you have excellent preoperative 
imaging and the ability to assess PTH levels intra-
operatively. If you have excellent imaging, you may 
consider a minimally invasive operation without 
intraoperative PTH, but you are placing the patient at 
risk for a second operation, a full neck exploration, if 
the 
hyperparathyroidism 
persists. 
Therefore, 
although it may be tempting to not perform a full 
neck exploration, we cannot recommend this strategy 
for low-resource settings. 
The indications for neck exploration in 
hyperparathyroidism include:  
● Proven parathyroid disease and no intraoperative 
PTH assay 
● Failed single gland exploration 
● Secondary hyperparathyroidism: as mentioned, 
the availability of cinacalcet may influence your 
surgical decision-making, especially in patients 
with significant comorbidities. 
● Tertiary hyperparathyroidism 
 
Imaging options for the parathyroid glands include: 
 
Ultrasound 
 
As in other areas in this Manual, we 
recommend that the surgeon become skilled at 
performing ultrasound. It is very helpful to be able to 
locate an enlarged gland using ultrasound in clinic, 
and then repeat it in the operating room immediately 
before surgery.  
 
Parasagittal (left) and axial (right) views show the typical oval, 
hypodense ultrasound appearance of a parathyroid adenoma, 
adjacent to the more dense tissue of the thyroid gland. Case 
courtesy of Dr Maulik S Patel, From the case  
https://radiopaedia.org/cases/16063?lang=us  
 
Computed Tomography Scan 
 
On CT scan of the neck with IV 
contrast, parathyroid adenomas are visible as 
hyperlucent compared to surrounding structures. The 
scan typically is performed in three phases: non-
contrast, arterial (30 seconds after contrast injection,) 
and delayed (60-90 seconds after contrast.) This is 
sometimes referred to as “4D CT,” with the 4th 
dimension being time. An adenoma will have low 
attenuation on non-contrast phase, light up promptly 
on arterial phase, and have decreased attenuation but 
still be visible on delayed phase.  
4D CT is not used in every case of 
hyperparathyroidism, but it is very useful in 
identifying parathyroid gland(s) in the reoperative 
setting. It is more sensitive and specific than either 
ultrasound or Sestamibi in localizing parathyroid 
glands.  
 
Three phases of CT scan of the neck showing a parathyroid 
adenoma in the right tracheoesophageal groove (Red arrow.) 
Left, non-contrast phase: The tumor has low attenuation. 
Center: arterial phase: The well-vascularized tumor has high 
attenuation.  
Right, delayed contrast phase: The tumor has low attenuation, 
though more than surrounding tissues. 
Case courtesy of Dr Jenny Hoang, from the case 
https://radiopaedia.org/cases/30418?lang=us  
 
Approach to Parathyroid Disease 
Richard Davis, Naira Baregamian, Courtney Gibson 
 
OPEN MANUAL OF SURGERY IN RESOURCE-LIMITED SETTINGS 
www.vumc.org/global-surgical-atlas 
This work is licensed under a Creative Commons Attribution-ShareAlike 3.0 Unported License  
 
 
CT scan with IV contrast in the delayed phase shows an ectopic 
parathyroid adenoma inside the chest, between the esophagus 
and the vertebral column (White arrow.) Case courtesy of Dr 
Andrew Lawson, from the case 
https://radiopaedia.org/cases/25631?lang=us  
 
Sestamibi Scan 
 
This radionuclide imaging technique will not 
be available in most low-resource settings. It consists 
of injection of Technetium-99 sestamibi (a 
shortening of “sesta-methoxyisobutylisonitrile,”) 
followed by measurement of radioactivity in the neck 
and upper chest. Scanning occurs at 15 minutes and 
2 hours following administration. At 15 minutes, the 
thyroid gland and the largest parathyroid adenoma 
will be seen. At 2 hours, only the adenoma will be 
seen. This technique is best used in conjunction with 
an ultrasound, both to verify that a lesion seen at 
ultrasound is indeed a parathyroid adenoma, and to 
locate any adenomas not seen by ultrasound.  
 
It is important to note that in the presence of 
two adenomas, only the larger one will be seen on 
Sestamibi scan. So the presence of only one tumor on 
the scan does not indicate that only one  parathyroid 
adenoma is present: as stated above, 15-20% of 
patients with primary hyperparathyroidism have 
multi-gland disease.  
 
Sestamibi scan at 15 minutes (Left) and 2 hours (Right) shows 
a parathyroid adenoma adjacent to the lower pole of the left 
thyroid gland (Arrow.) At the early images, the thyroid gland is 
also seen but at 2 hours the adenoma alone is seen. The other 
black masses above the thyroid glands are the submandibular 
salivary glands. Case courtesy of Dr Jörgen Strömberg, from 
the case 
https://radiopaedia.org/cases/54793?lang=us  
 
Decision Making: 
In patients with hypercalcemia, we perform a 
careful history and thorough physical examination 
with emphasis on masses in the neck. A palpable 
neck mass raises concern for parathyroid carcinoma, 
especially if the Calcium level is more than 
12mg/dL.  
A history of dialysis or renal transplantation 
raises the likelihood of secondary or tertiary 
hyperparathyroidism.  
 
In all cases, an elevated parathyroid hormone 
level confirms the diagnosis. If it is normal or low, 
consider the other causes of hypercalcemia listed 
above under “Physiology and Anatomy.” In true 
primary hyperparathyroidism, both the serum 
calcium and the parathyroid hormone must be 
elevated. Isolated hypercalcemia with a low PTH is 
often due to occult malignancy. 
For patients with chronic abdominal pain, if 
the history and physical does not yield any suspected 
diagnosis, we will check a serum Calcium level, 
Thyroid Stimulating Hormone level, Complete 
Blood Count and Erythrocyte Sedimentation Rate as 
part of our workup. This situation is discussed 
elsewhere in this Manual.  
Once the diagnosis of hyperparathyroidism is 
confirmed, surgical planning begins. A meticulous 
neck exploration by an experienced surgeon is better 
than any imaging. If you do not have any of the 
Approach to Parathyroid Disease 
Richard Davis, Naira Baregamian, Courtney Gibson 
 
OPEN MANUAL OF SURGERY IN RESOURCE-LIMITED SETTINGS 
www.vumc.org/global-surgical-atlas 
This work is licensed under a Creative Commons Attribution-ShareAlike 3.0 Unported License  
 
advanced imaging mentioned in this chapter, you 
may still perform an ultrasound to help guide your 
exploration. Even if you are certain where the tumor 
is after ultrasound, we still recommend you perform 
a 4-gland exploration as described in the following 
chapter.  
If you are faced with a patient who has 
persistent 
hyperparathyroidism 
after 
a 
neck 
exploration, be very cautious. Such patients are best 
treated by an expert in endocrine surgery. If you are 
the patient’s only option, try to get a well-performed 
“4D CT” scan. We refer the patient to a facility 
where we know the scan will be done well, and we 
discuss with the radiologist or radiographer 
beforehand. Search carefully in the areas described 
in this chapter.  
For 
secondary 
and 
tertiary 
hyperparathyroidism, your main goal is to “debulk” 
the patient’s hypertrophic parathyroid glands. You 
will remove 3½ of the four glands. There are various 
options for the remaining parathyroid tissue, as 
described in the chapter.  
 
Richard Davis MD FACS FCS(ECSA) 
AIC Kijabe Hospital 
Kenya 
 
Naira Baregamian, MD, MMS, FACS 
Vanderbilt University 
Tennessee, USA 
 
Courtney E. Gibson, MD, MS, FACS 
Yale University 
Connecticut, USA 
 
 
 
 
 
 
 
 
 
 
 
 
Resource-Rich Settings 
• 
Preoperative imaging techniques such as 99Tc-
SESTAMIBI,  99Tc-SESTAMIBI-SPECT, 4D CT 
neck with and without contrast (parathyroid 
protocol) can be employed for preoperative 
parathyroid localization and identification of the 
ectopic and mediastinal parathyroid gland(s). 
• 
Parathyroid angiography can be used in cases of 
failed multiple parathyroid surgeries and require  
venous PTH sampling for localization.  
• 
Intraoperative parathyroid hormone (IOPTH) 
monitoring is routinely utilized to confirm 
intraoperative biochemical cure following 
parathyroidectomy. 
• 
Intraoperative nerve monitoring of the recurrent 
laryngeal nerve is prudent in re-operative setting 
and during resection of a parathyroid mass 
concerning for malignancy. 
• 
Intraoperative use of near infrared parathyroid 
autofluorescence technology can aid in parathyroid 
identification and preservation. 
