Ch 121 thyroid and parathyroid Flashcards
Anatomy
- two thyroid glands
- cranial pole at level of cricoid cartilage
- right gland is in close proximity to (carotid sheath)
- laryngeal recurrent nerves are positioned dorsally and medial to thyroid
- vascular supply to the thyroid gland is mostly through cranial (common carotid) and caudal thyroid arteries
- Lymphatic drainage is to cranial deep cervical lymph node or medial retropharyngeal
What is unique about the thyroid blood supply of the cat?
In most cats, the caudal thyroid artery is absent
Into what structures does the lymph of the thyroids drain?
Right: Right lymphatic duct
Left: Tracheal duct
parathyroid glands
- external parathyroid gland x 2 and internal parathyroid gland x 2 per thyroid
- ## Variations in location, number, and distribution of parathyroid glands are frequently reported.
Where is ectopic thyrpid tissue commonly found?
ectopic parathyroid
Along the trachea
Thoracic inlet
Within mediastinum
Thoracic portion of the descending aorta
parathyroid: 35% to 50% of cats, 3% to 6% of dogs
How are thyroid hormones produced?
- Thyroglobin produced within the thyroid and stored within the thyroid follicle (Sufficient iodine is necessary for production of thyroglobin)
- thyroglobulin, a glycoprotein containing iodotyrosines that serve as precursors
- Thyroglobin moves into follicular cells and is hydrolysed into thyroxine (T4) and triiodothyronine (T3) which are released into the blood
What % of T3 and T4 circulate unbound to protein?
Less than 1%
Protein-bound thyroid hormones serve as a large reservoir
Which thyroid hormone is more biologically active?
T3
Approx 40-60% of T3 is derived from monodeiodination of T4 in peripheral tissues
What substances regulate thyroid hormone synthesis?
- Thyrotropin (TSH) from the pituitary gland
- TSH major modulator of thyroid gland activity, secreted by the pituitary gland, inhibited by thyroid hormone in a negative feedback regulatory mechanism
- Thyrotropic-releasing hormone (TRH) from the hypothalamus. Modulates thyroid hormone-TSH feedback loop
Where is PTH made?
PTH is synthesised, stored and secreted by chief cells of the parathyroid gland
What are the main effects of PTH?
- Increase Ca concentration
- Decrease phosphorus conc
- Bone: Ca and phosphate reabsorption
- Kidneys: Rapid decrease in excretion of Ca and increase in excretion of phosphorus. Increased formation of 1,25-dihydroxycholecalciferol (calcitriol) from Vit D
- Intestines: Calcitriol increases absorption of Ca and phosphorus
- Ionized calcium (Ca2+) is the physiologically active form (high calcium inhibits PTH secretion (negative-feedback homeostatic control)
Other than PTH, what other hormone is involved with Ca homeostasis? How does it work?
- Calcitonin (produced by thyroid gland parafollicular C-cells)
- Prevent postprandial hyperCa by decreasing bone resorption but has no effect at level of kidneys or intestines
What % of hyperthyroidism in cats is caused by carcinoma?
1-4%, mets in up to 71%
(Usually adenomatous hyperplasia)
Histologic features that distinguish adenocarcinoma from benign adenoma in cats are degree of capsular and vascular invasion, mitotic, mets
How common is bilateral involvement of hyperthyroididm in cats?
How common is ectopic thyroid seen?
Bilateral in approx 70%
Ectopic hyperfunctioning tissue in 9-23%, most commonly in the chest
List concurrent diseases often seen with hyperthyroidism in cats
excess secretion of T4 can lead to multisystemic disease
Cardiac disease
- Tachycardia, murmurs, gallop, HCM, sometimes hypertension
Renal dz
- Pre-existing renal insufficency in up to 40%.
- Renal blood flow, glomerular filtration rate, and renal tubular capacities can be affected
- Hyperthyroidism can mask preexisting chronic renal insufficiency
- Trial course of methimazole recommended prior to any irreversible treatments
Hypokalaemia
- in 32%
* Stress-induced release of catecholamines
* neck ventroflexion
What imaging method is most useful for diagnosis and anatomical localisation of hyperfunctioning thyroid tissue?
Scintigraphy
- Technetium 99m - pertechnetate (99mTcO4)
- Trapped by thyroidal iodine-concentrating mechanisms
- Does not reflect function
- Pertechnetate normally concentrates in thryoid, salivary and gastric mucosa
- Because of negative feedback on the pituitary gland, all normal thyroid tissue should be completely atrophied in a hyperthyroid cat > hyroid activity in a hyperthyroid cat should be interpreted as active adenomatous or cancerous tissue
What is the main goal of pre-op treatment of hyperthyroid cats?
- treated medically to achieve a euthyroid state nd control the adverse effects of the disease on the heart
- Methimazole or propylthiouracil until euthyroid (6-12wks pre-op)
- methimazole block synthesis of thyroid hormones by inhibiting organification of iodide and coupling of iodothyronines to form T4 and T3
- If azotaemia occurs, lifelong methimazole recommended, no irreversible treatments
- tachycardia prevents good coronary perfusion, which occurs during diastole
- beta-antagonist (propranolol or atenolol) slow the heart rate, improve stroke volume, and increase cardiac output
anaethesia
- avoid stimulate or potentiate adrenergic activity (adrenalin/NA)
- ketamine, halothane, and atropine
- acepromazine should not be used in hypovolemic or dehydrated cats
- Rapid metabolic rate can increase the absorption, distribution, tissue uptake
- hypokalemia should receive potassium supplementation
What muscles must be seperated on the approach to the thyroid?
Sternohyoid
Sternothyroid
Sx approach
- abnormal thyroid gland can be located dorsal to the cranial trachea or caudally near the thoracic inlet
- external parathyroid gland: spherical, 1 to 3 mm in diameter, paler, ventral surface of the cranial pole
- unilateral disease > surgery is a reasonable treatment because risks are low compared with bilateral disease
List the surgical options of thyroidectomy
Intracapsular
- incision into the thyroid capsule and blunt dissection of the parenchyma to separate it from the capsule and remove it, leaving the capsule in situ
- high recurrence
Extracapsular
- gland is removed with its capsule > no attempt to save parathyroid
- high rate of hypoparathyroidism in animals with bilateral disease
Modified extracapsular
- thyroid capsule is incised around the external parathyroid gland while preserving the parathyroid branch of the cranial thyroid artery
- Blunt dissection of the thyroid parenchyma is performed (cotton tip)
- then capsule removed, fine scissors is used to cut the capsule around the external parathyroid gland to preserve it
What cand be done if a parathyroid gland is accidentally removed or its blood supply is damaged?
Reimplantation into a pocket of sternohyoid or sternothyroid muscle
- Function expected within 7-21d
- after bilateral thyroparathyroidectomy, 87% of cats did not require postoperative calcium
- concerns about the risk of transplantation of diseased thyroid
Staged Bilateral Thyroidectomy
- allows time for the blood supply of the ipsilateral parathyroid gland
- decreases the incidence of postoperative hypocalcemia but requires two anesthetic episodes.
List potential complications of thyroidectomy
prognosis for cats treated by thyroidectomy is excellent
Hypoparathyroidism
- bilateral less than 6%
- rare unilateral
- occurs even if ectopia present
Hypothyroidism
- rare, even after bilateral
- likely will not be needed long term because of accessory thyroid tissue,
- supplementation may improve renal function in hypothyroid azotaemic cats
Recurrence
- 5-11% within 2-3yr
- dt ectopic or residual tissue > perform scintigraphy
- best treatment for ectopic tissue is radioactive I131
Haemorrhage
Lar par
Horners syndrome
Dyspnoea
clinical signs of hypoCa
- restlessness, facial or generalized muscle twitching, weakness, anorexia, panting, tetany, or convulsions
- may occur 12 hours to 6 days postoperatively
- Only 60% of cats with severe hypocalcemia (total calcium <6.5 mg/dL or ionized calcium <0.8 mmol/L) demonstrate clinical signs
How do you treat acute hypoCa?
0.5-1.5ml/kg 10% Ca gluconate slowly IV, with ECG monitoring
Followed by CRI of Ca gluconate at 5-15mg/kg/hr IV
Alternatively 10ml 10% Ca gluconate added to 250ml bag and administered at 60ml/kg over 24hr
- Do not add Ca to LRS as it precipitates
- Do not used Ca carbonate IV or SQ
What is prescribed for maintenance therapy of hypoCa?
For how long?
- Oral Vit D (calcitriol) and calcium
- up to 3 months. Monitored weekly and tapered as required
With autotransplantation, hypocalcemia usually resolves within 21 days; without, can last up to 3 months
goal is to maintain the serum calcium concentration in the low-normal range (8.5 to 9.5 mg/dL).
This prevents clinical signs of hypocalcemia while still stimulating growth and function
What is the prognosis for thyroid carcinoma
- Rare so relatively unknown
- Marginal thyroidectomy + I131 - survival 10-41m
- High dose I131 alone - 6/8 euthyroid with survival time 181-2381d
List alternative treatments for hyperthyroidism in cats
- Methimazole or carbimazole
- Iodine-restricted diets (y/d) - 75-90% become euthyroid
- Radioactive iodine (I131) - Tx of choice. Single dose results in cure in most and ectopic tissue is also treated (considered carefully in regard to renal function)
What % of clinically detectable thyroid masses in dogs are malignant?
Bilateral?
Metastasise?
Functional?
- 90% thyroid carcinomas
- 25-47% bilateral
- Up to 40% mets a diagnosis, 80% develop mets
- 10-29% hyperthyroid
tumor biology
- in necropsy studies, 30% to 50% of thyroid tumors are benign adenomas
- 90% of thyroid tumors detected clinically are malignant
- large; poorly encapsulated; and extend locally into or around the trachea, esophagus, and muscles of the neck
- highly vascular and invade local blood vessels.
- Approximately 25% to 47% of thyroid carcinomas are bilateral
- 13% are ectopic thyroid tissue at the base of the tongue, ventral neck, cranial mediastinum, or heart base
- two distinct groups of thyroid tumours are recognised, based on degree of mobility and local invasiveness
- Thyroid carcinomas appear to be poorly to moderately sensitive to chemotherapeutic agents
classified
- papillary, follicular, compact, or anaplastic
- most common: follicular and compact
mets
- 40% detectable metastatic disease at presentation
- 80% develop metastasis during the course of the disease
- lungs and regional lymph nodes (retropharyngeal lymph nodes the most common sites)
- viscera, brain, spinal cord, and skeleton
functional
- 10% to 29% are hyperthyroid
- 60% are euthyroid
- commonly interpreted as functional if there is clinical and/or laboratory evidence of hyperthyroidism. Most canine thyroid carcinomas are not in fact hypersecretory
- most have follicular elements and are capable of trapping and organifying radioiodine.
- human medicine the term ‘functional’, when applied to thyroid tumours, refers to the ability of
the neoplastic tissue to trap and organify radioiodine
- Judging the ‘functional’ ability of a tumour and whether radioiodide therapy is a rational option
for treatment based only on hypersecretion of thyroid hormones is inappropriate (worth 2005)
- Tumour ‘functionality’ can only be accurately assessed with thyroid scintigraphy
Breeds with an increased odds ratio for thyroid tumors
Golden Retrievers, Beagles, and Siberian Huskies
Dx
- palpable mass, dyspnea, dysphagia, change in bark, and facial edema
- Palpation is not very accurate to determine local invasion
- ultrasonography, CT, and MR cannot be absolutely definitive regarding mass resectability > sx exploration more definitive
Ultrasonography
- determination of the origin of the mass
- whether the condition is bilateral
- information regarding invasiveness and, by use of pulsed or color-flow Doppler, vascularity.
CT
- determine origin, invasiveness, and vascularity of the mass and the presence of metastasis
- highly specific for determining histopathologic invasion of thyroid tumors (100%) but MRI is more sensitive for this purpose (93%)
Cytology and Biopsy
- usually adequate to confirm that the mass is of thyroid origin
- cyto not a reliable means to distinguish between benign and malignant
- Tru-Cut is not recommended because of the high risk of severe, and sometimes fatal, hemorrhage
How can iodinated contrast material used for CT scan effect further diagnostics and treatment?
Inhibitory effect on thyroid uptake of radioiodine and pertechnetate
What blood tests are required to determine the functional status of a thyroid tumour in dogs?
Total T4
Free T4
TSH
Scintigraphy
- pertechnetate ion is trapped by the thyroidal iodide-concentrating mechanism, highlighting glandular tissue
- scintigraphy can be used to determine if a mass is of thyroid origin.
- poorly circumscribed on scintigraphy are more likely to be invasive.
- also helpful for identifying ectopic tissue
- Scintigraphy has been suggested as a means to determine the likelihood of response to I131 treatment, this is only true, however, when using a tracer that is incorporated into organic thyroid hormone
pre-op
- minimum database
- staged with three-view chest radiographs and abdominal ultrasonography/CT to assess l.n.
- cross-match for blood transfusion
- dogs with hyperthyroidism do not need treatment to induce euthyroidism
surgery
- freely movable defined as ≥1 cm in all planes during palpation
- Large or invasive tumors tend to be excessively well vascularized and can potentially invade or incorporate the jugular vein or carotid artery, requiring ligation of these vessels.
- Bilateral carotid artery ligation can be performed in dogs because of extensive collateral development but when performed acutely, it may result in intraoperative tachycardia and hypertension
- cautery, hemoclips, ligasure, harmonic scaler
- thyroidectomies in dogs are performed with a marginal excision, and a complete excision is often achieved
- The ability to attain an adequate margin of normal tissue depends on the structures
- structures within the carotid sheath, and laryngeal recurrent nerve > possible to sacrifice these unilaterally with acceptable morbidity because unilateral Horner’s syndrome and laryngeal paralysis usually do not affect quality of life.
- unilateral vagus sacrifice usually no problem
- Bilateral cervical vagotomy leads to high morbidity and mortality in dogs
- Marginal excision of thyroid tumors can lead to excellent local tumor control; therefore, dissection of critical structures off the tumor, rather than transection or resection of them, is recommended.
poor sx candidates
- bilateral fixed lesions because of high postoperative morbidity, including laryngeal paralysis, megaesophagus, and aspiration pneumonia from damage to nearby nerves
- tumor invades the esophagus or trachea
What intraop technique can aid in the identification of the parathyroid tissue?
Indocyanine green near-infrared fluorescent imaging
sx technique
- freely movable tumors tend to remain within the natural capsule
- When the tumor is unilateral, no attempt should be made to preserve these glands because of the greater risk of leaving tumor cells and ypoclacemia not concern
- With bilateral disease > prepared to treat the dog for postoperative hypoparathyroidism
- if a parathyroid gland can be identified and preserved, this should and can be done
post-op
- If significant nerve damage occurred during the surgery or if bilateral thyroidectomy was performed, the dogs are monitored for laryngeal paralysis and other complications
How often should Ca be monitored in dogs undergoing a bilateral thryoparathyroidectomy?
At least daily for 3-7 days with Ca and Vit D supplementation
List treatment options for thyroid carcinoma
Surgical excison (freely movable most amenable)
Radiation therapy
Radioactive I131
List potential complications after thyroidectomy in dogs
- Haemorrhage and anaemia
- Hypothyroidism (40% if bilateral)
- Laryngeal paralysis
- Megaoesophagus (bilateral vagus)
- Hypoparathyroidism and hypocalcaemia (21/27 dogs with bilateral thyroparathyroidectomy). Many require lifelong therapy
List prognostic factors associated with thyroid carcinoma
- Mobility (resectability/margins)
- Size
- Stage of disease
- Vascular invasion
- benign (adenoma, sx can be cure)
Overall MST 22m
Even with incomplete margins, the prognosis can be excellent.
List factors associated with thyroid carcinoma invasiveness
- Diameter
- Volume
- Fixation
- Ectopic location
- Follicular cell origin
MST 3yr if freely movable vs 6-12m if more invasive
List factors assoc with metastasis with thyroid carcinoma
Bilateral disease and tumour size
- 14% if less than 23cm^3
- 100% over 100cm^3
Bilateral tumours are 16x more likely to met
What percentage of dogs with thyroid carcinoma have ectopic tumors?
What are the most common locations?
13% ectopic tumour
- Sublingual (may require partial hyoidectomy)
- Cranial mediastinal
Tx with surgical excision, I131 or external beam radiation therapy
median survival time of dogs with untreated thyroid carcinoma
3 months
radioactive iodine
- nonresectable or incompletely resected thyroid
- Thyroid tumors do not need to be functional to respond to I131 treatment
- radionuclide scan aid in the determination of the likelihood of response > tumors that do not adequately concentrate the radioisotope are less likely to respond to therapy
- MST without metastatic disease was 839 days
- MST with metastasis 366 days
- Three dogs (8%) died of I131-induced myelosuppression
medullary thyroid carcinomas = C-cell tumours – do not take up iodide or produce T4
Radiation
- invasive or incompletely resected tumors
- nonresectable tumors (48 Gy (4 Gy/fraction) had a mean progression-free survival of 45 months and 3-year progression-free survival rate of 72%
- 96 weeks for dogs with pulmonary metastases and 127 weeks for those without
Chemotherapy
- role of adjuvant chemotherapy poorly defined.
- doxorubicin or cisplatin, 30% to 50% demonstrated a partial response
Ectopic Thyroid Tumors
- Tumors in the cranial mediastinum: surgically excised, I131 or radiation therapy.
- tumors that involve the heart are typically intracardiac and therefore challenging to surgically excise
- tumors in the sublingual area can be amenable to surgical excision
- The hyoid apparatus is often involved > basihyoid bone appears to be the one most common
- MST surgery (873 days) was significantly longer than not receive surgical treatment (481 days)
- results may reflect size of the mass, the presence of metastatic disease, or tumor type.
Partial Hyoidectomy
- excision of the basihyoid bone and variable portions of the thyrohyoid, epihyoid, and ceratohyoid bones would be expected to have negative consequences on laryngeal and pharyngeal function
- Placement of hyoid apparatus–stabilizing sutures is an attempt to ameliorate
- Dogs tolerate partial hyoidectomy very well.
- no signs of dysphagia, ptyalism, or abnormal tongue carriage
List the systemic effects of hypothyroidism which may effect anaesthesia/surgery
Cardiovascular
- Decreased contractility
- Increased vascular resistance
- Decreased vascular volume
- Artherosclerosis
Suppression of humoral immune response, impariment of T-cell function and reduction in number of circulating lymphocytes
Effect on wound healing varies by species but may disturb fibroblast deposition of collagen, keratinocyte proliferation
euthyroid sick syndrome, TSH is usually within the normal
What causes primary and secondary hyperparathyroidism?
Primary - Excessive production and secretion of PTH by abnormal, autonomously functioning parathyroid chief cells. Keeshond predisposed. Maybe also Siamese
Secondary:
- Renal secondary hyperparathyroidism
- Nutritional secondary hyperparathyroidism - imbalances in phosphorus, Vit D or Ca
Hyperparathyroidism
- Most nodules in dogs are adenomas or adenomatous hyperplasia;
- up to 5% are carcinomas
- 90% of dogs and cats have 1 nodule
- 42% of dogs had 2 abnormal glands
- RARE > all 4 glands hyperplastic, secondary hyperparathyroidism suspected.
- Metastasis rare
- Ectopic parathyroid adenocarcinoma has also been reported in the cranial mediastinum
What are the pathophysiologic effects of primary hyperparathyroidism?
Skeletal effects
- PTH-induced resorption of Ca2+ from bone
- Fibrous osteodystrophy (skull)
- Pathologic fractures
Renal effects:
- Renal tubular mechanisms become overwhelmed and excessive Ca excretion results (despite high PTH)
- Urolithiasis, UTI, PU/PD, diabetes insipidus
- Hypercalcemia can decrease renal function by two means
- If Ca x P product is greater that 60-80 mg/dL, soft tissues calcify, causing renal dysfunction
- Renal vasoconstriction and decreases renal blood flow.
- production of vitamin D also increases, exacerbating hypercalcemia.
About 4% of dogs with primary hyperparathyroidism will have renal damage
List DDx for hyperCa
HARDIONS
Hyperparathyroidism (primary and secondary)
Addison’s (hypoadrenocorticism)
Renal failure (acute and chronic)
Vitamin D toxicity
Idiopathic (cats) or infection (granulomatous disease, eg. fungal disease)
Osteolysis (rare; reported with osteomyelitis and hypertrophic osteodystrophy)
Neoplasia (lymphoma, MM, anal-sac adenocarcinoma)
Spurious (lab error, excessive supplementation, etc.)
Dx
- nodules can be palpated in 50% of affected cat
- normal ionised Ca: 1.1mmol/l - 1.4mmol/l
- ideally check PTH, and PTH–related peptide (PTH-rp) concentrations
ultrasound
- normal are hypo-anechoic
- parathyroid nodules as small as 0.5 cm in diameter can be detected
- very accurate, but negative ultrasound results do not rule out a tumor
scintigraphy
- double-phase parathyroid scintigraphy had poor sensitivity and specificity > not recommended
How is primary hyperparathyroidism diagnosed?
How is this differed from renal secondary hyperparathyroidism?
Inappropriate PTH (normal or high) on the face of increased ionised Ca. Low PTH-rp
- Differes from CKD (renal secondary hyperparathyroidism) as primary hyperparathyroidism will have decreased phosphate (as apposed to elevated) and are not azotaemic.
- Patients with increased PTH-rp should undergo further diagnostics for neoplasia
- PTH-rp may also be elevated in dogs with CKD without malignancy
- hypercalcemic and have [PTH] within the reference range are still considered to have excessive PTH
When is pre-op medical management recommended prior to Sx for hyperparathyroidism?
What does this encompass?
Medicam management if concurrent renal failure or Ca-phosphorus ratio greater than 60-70
- Saline diuresis 120-180ml/kg/d
- Furosemide
- K supplementation PRN
- If above fails, glucocorticoids can promote calciuresis
- If all above fails, bisphosphonates or calcitonin
What are the surgical options for external parathyroidectomy and internal parathyroidectomy?
External:
- Parathyroidectomy
- Partial thryoidectomy (guillotine technique, ensure preserve blood supply to rest of thyroid)
Internal:
- Partial thyroidectomy (ipsilateral external parathyroid gland should be preserved)
- If carcinoma, complete thryoparathyroidectomy
cystotomy to remove the calculi can be done under the same anesthesia
List methods of intra-op detection of abnormal parathyroid glands
Intra-op measurement of PTH with rapid chemiluminescent assay
- Decrease by less than 50% baseline after 10 mins indicates autonomously function tissue remaining
- not alwyas accurate
IV methylene blue
- Dose required has too high a risk of toxicity (Heinz body anaemia and acute renal failure)
- NOT recommended
Indocyanine green near-infrared imaging
- promising experimentally
some delay Sx if the affected parathyroid gland cannot be identified preop by an experienced ultrasonographer (repeat u/s until larger)
ectopic anatomic location
Excision of Multiple Abnormal Glands
Three of four parathyroid glands can be safely removed without a risk of permanent hypoparathyroidism
post-op
Fluids & Analgesia
Calcium Monitoring:
- Serum total or ionized calcium checked 1-2 x daily for 5-7 days.
- Preoperative calcium levels may or may not predict postoperative hypocalcemia.
Calcitriol Therapy:
- Some protocols start calcitriol only if preoperative calcium is high (>1.75 mmol/L).
- Others recommend starting calcitriol for all dogs
- Tx can last up to 2 months, requiring frequent monitoring.
Weaning Off Calcitriol:
- Initial doses: 20-30 ng/kg in the morning and 10-15 ng/kg in the evening of surgery.
- Gradual reduction by 10% every 4 days over 45-60 days while monitoring calcium levels.
- Adjustments needed if (Ca <0.95 mmol/L ionized) or too high.
Exercise Restriction:
- Dogs: At least 6 days to prevent tetany from hypocalcemia.
- Cats: Kept indoors for 14 days.
List potential complications after parathyroidectomy
HypoCa
- 35-70%,
- 25% of which develop clinical signs between 12hr-20d (most commonly within 1 week)
- all four parathyroid removed > life long Tx (only 3% to 6% of dogs have accessory parathyroid tissue)
- tx if CS or <0.95mmol/L
- acute Tx: 0.5 to 1.5 mL/kg slowly to effect, monitored by ECG for bradycardia and arrhythmias
- maintenance: 10 mL of 10% calcium gluconate in a 250-mL bag of 0.9% sodium chloride solution and administer it at 60 mL/kg/day IV
- long-term: Calcitriol is the vitamin D 0.005 to 0.015 µg/kg/d divided twice daily, oral elemental calcium is 25 to 50 mg/kg/d divided into 2 to 3 daily doses
Recurrence
- 8% within months to years.
- Second surgery usually highly successful
- dt multiglandular disease, ectopic glands, incomplete removal or metastasis
Overall prognosis is excellent, even with parathyroid carcinoma (Hyper Ca resolved in 44/47 with median follow up of 561d)
List alternative therapies for primary hyperparathyroidism
- Ultrasound guided ethanol ablation
- Ultrasound-guided heat ablation
Inconsistent results
Comparison of survival times of cats with hyperthyroidism treated with thyroidectomy or methimazole
at a primary care hospital in Japan
Eiji Naito 2024
41 cats
thyroidectomy (n = 15) and methimazole (26)
survival time was significantly longer with thyroidectomy (1893d) than with methimazole (730d)
The recurrence rate was significantly lower in cats that underwent thyroidectomy
Alendronate treatment in cats with persistent ionized
hypercalcemia: A retrospective cohort study of 20 cases
Maxime Kurtz
JVIM
Alendronate overall was well tolerated with
chronic use in this cohort, and can be considered a treatment option for persistent
ionized hypercalcemia in cats
use of glucocorticoids (or furosemide)
usually is reserved for short-term treatment of severe symptomatic
Bisphosphonates inhibit
osteoclastic activity by altering intracellular protein trafficking and
perturbing normal cytoskeleton physiology,16 which results in
decreased bone resorption and decreased calcium release
Tsimbas 2019 – palliative-intent hypofractionated RT for non-resectable thyroid carcinoma
- response rate: 5/20 (25%) - 2/20 (10%) complete, 3/20 (15%) partial
- overall MST 170d (1-824)
- overall survival only associated with complete/partial response
Surgical description and outcome of ultrasound-guided minimally invasive parathyroidectomy in 50 dogs with primary hyperparathyroidism
Young 2023
Animals: Fifty client-owned dogs with PHPT that underwent minimally invasive
parathyroidectomy.
Study design: Retrospective cohort study
ultrasound-guided mini lateral approach. Abnormal parathyroid
glands were removed en bloc via partial thyroidectomy.
17 hyperplastic glands (17/62, 27.4%), 34 adenomas (34/62, 54.8%), and two carcinomas(2/62, 3.2%).
Hypercalcemia resolved shortly after surgery in 44 dogs (97.8%). One dog had recurrent hypercalcemia (1/45, 2.2%), one dog had persistent
hypercalcemia (1/45, 2.2%), two dogs had permanent hypocalcemia and one dog died
from clinical hypocalcemia (1/45, 2.2%).
hungry bone syndrome (HBS).33 HBS is encountered in humans that have a high preoperative bone turnover rate
star retractor and bipolar
Ambidirectional cohort study on the agreement of
ultrasonography and surgery in the identification of
parathyroid pathology, and predictors of postoperative
hypocalcemia in 47 dogs undergoing parathyroidectomy
due to primary hyperparathyroidism
Burkhardt 2021
- u/s and surgery agreement: number of affected glands 31/47 (65.9%) affected side 34/47 (72.3%)
- u/s cut-off ≥8.0mm → distinguished malignant from benign
- surgical exploration of both sides recommended –
- surgeons were found to be more successful
at identifying parathyroid pathology > but 23.4% normal tissue excised - pre-op iCa ≥1.75mEq/L → 7.5x greater odds of post-op hypocalcemia
- 47% subclinically hypocalcemic, 17% clinically hypocalcemic post-op
- prophylactic calcitriol/calcium supplementation → not associated
This inconsistency in identifying parathyroid
pathology on ultrasonographic examination may
explain the previous reports of inferior cure rates of ultrasound
guided parathyroid gland ablation when compared
with surgical excision; approximately 70% versus 95%, respectively.
In conclusion, ultrasonography is only a moderately
reliable tool in evaluating parathyroid pathology
Metastasis to ipsilateral medial retropharyngeal and deep cervical lymph nodes in 22 dogs with thyroid carcinoma
Owen T. Skinner 2021
To determine the rate of nodal metastasis to the medial retropharyngeal
(MRP) and deep cervical lymph nodes in dogs surgically treated for
thyroid carcinoma.
Study design: Retrospective study.
Animals: Twenty-two client-owned dogs
Metastases were identified in 14 lymph nodes in 10 of 22 (45%) dogs.
All four excised deep cervical lymph nodes and one contralateral MRP lymph node were identified as metastatic
Regional metastasis was common within the lymph nodes sampled
in this population of dogs with thyroid carcinoma.
Use of a vessel-sealing device versus conventional
hemostatic techniques in dogs undergoing thyroidectomy
because of suspected thyroid carcinoma
Maxime Lorange 2019
Retrospective cohort study.
ANIMALS
42 client-owned dogs
Hemostatic technique (ie, use of a VSD vs conventional hemostatic
techniques) was the only factor significantly associated with operative duration
(median time, 28 vs 41 minutes). Postoperative hospitalization times
and complication rates did not differ between groups.
VSD, rather than conventional hemostatic
techniques, in dogs undergoing thyroidectomy because of suspected thyroid
carcinoma resulted in shorter operative times without significantly affecting
complication rates or postoperative hospitalization times
Major complications were reported in 3 dogs
in which conventional hemostatic techniques were
used. One dog developed acute bleeding from the
surgical incision 3 hours after the procedure
Four dogs in which a VSD was used had major
complications. One dog had iatrogenic esophageal
perforation when the esophagus was inadvertently
included in the jaws of the VSD.
Two dogs developed aspiration pneumonia
Complications and outcomes associated with unilateral
thyroidectomy in dogs with naturally occurring
thyroid tumors: 156 cases (2003–2015)
Jennifer K. Reagan 2019
complications occurred in 31 of the 156 (19.9%)
dogs; hemorrhage was the most common intraoperative complication (12
[7.7%] dogs). Five of 156 (3.2%) dogs received a blood transfusion
aspiration pneumonia (5 [3.2%] dogs) > In 2 of the dogs with aspiration pneumonia, laryngeal examination revealed bilateral laryngeal paralysis.. One hundred fifty-three of 156 (98.1%) survived to discharge from the hospital.
most lost to follow up > median survival time was 911 days
Overall postoperative metastatic disease or local recurrence developed
in 22 dogs.
perioperative mortality rate of 3.4%. and a complication rate of 19.9%.
were euthanized because reconstruction of the larynx was not possible
gross vascular invasion and lymph
node metastasis were recorded for 54 (34.6%) and 11 (7.1%) of the 156 cases, respectively
capsular invasion (96/156 [61.5%] dogs
Factors that were associated with the overall complication rate included duration of hospitalization and
whether the mass was assessed as fixed or mobile
during physical examination. The odds of developing complications for dogs with a fixed mass were 5.4 times the odds for dogs with a mobile mass
In the present study, only 15 of 130
(11.5%) tumors that were classified were considered
fixed, which likely represented a treatment bias
cervical CT can help guide surgical
decision-making; nevertheless, cervical exploratory
surgery should be considered because most of the
fixed tumors were still removable.
The 2 factors that were significantly associated
with a shorter progression-free interval were mitotic
index (hazard ratio, 1.24; 95% CI, 1.09 to 1.41; P <
0.001) and the maximal dimension of the tumor
Outcomes for dogs with functional thyroid tumors
treated by surgical excision alone
Alyson N. Frederick
27 client-owned dogs
hyperthyroidism
secondary to thyroid neoplasia
Most
tumors (23/27 [85%]) were malignant. Estimated median survival time was
1,072 days. No significant prognostic factors were identified. One dog had metastatic disease at the time of diagnosis (4%)
recurrence in 1 dog
Survival time for the dog with metastatic dis
ease at the time of diagnosis was 87 days
Thirteen (48%) dogs, includ ing
all 5 dogs that underwent bilateral thyroidecto
my, required lifelong administration of supplemental thyroid hormone
Dogs with resectable functional thyroid tumors had a good prognosis with
surgical excision alone.
dogs with functional thyroid tumors treated with
surgical excision alone have survival times compa
rable to historically reported survival times for dogs
with all thyroid tumors
clinical signs attributable to hyperthyroidism may
contribute to earlier detection of thyroid tumors
Clinical features and outcome of
functional thyroid tumours in 70 dogs
V. F. Scharf 2020
Median survival time was 72.6 months
for dogs treated with surgical excision and 15.7 months for dogs that did not receive surgery
54% showed Clinical signs
16% bilateral
18% ectopic
23% described as fixed
96%) received either definitive or pallia
tive treatment, which, for the purposes of this study, included surgical excision, radiation, chemotherapy, methimazole administration or a combination
64% developed hypothyroidism after surgery.
Dogs with functional thyroid tumours may survive a long time after surgical
excision, although post-operative hypothyroidism is common
Peri-operative complications were responsible for the deaths of four dogs
dogs treated with surgical excision of the thyroid tumour appear to have better survival.
neoplastic tissue rather than dif fuse
hyperplasia is the primary contributor to hyperthyroidism in dogs with thyroid-associated hyperthyroidism
Athey 2024 – review of thyroid carcinomas with focus on compact subtype and medullary type
- follicular thyroid carcinoma (FTC) or medullary thyroid carcinoma (MTC)
- MTC prevalence 5-36%
- FTC → follicular, follicular-compact/mixed, compact and papillary subtypes
- biologic behaviour:
- metastasis: regional LN 14-26%; distant 20-38%; overall 18-95%
- FTC → lung via cranial/caudal thyroid veins
- MTC → cervical LN
- treatment: I131
uptake related to degree of differentiation
- MTC may not take up I131
but effect may be from adjacent follicular cell uptake
- prognosis: good-excellent; MST: sx alone 7-36+ months; untreated 3 months
pathology
Townsend 2022 - review
- fixed tumours → 5.4x increased risk of complication
- metastasis: LN: 7.1-45%
- prognosis:
- negative indicators: fixed tumour – MST 6-12m vs 3y
large tumour dimensions → shorter DFI/no effect on survival
→ higher rate of metastasis
vascular invasion, Ki-67, mitotic index (DFI and ST)
higher WHO stage
- positive indicator: surgical excision
- not associated: tumour functionality
Merkle 2021 – thyroid storm in a dog with thyroid carcinoma
- thyroid storm (thyrotoxic crisis): excess circulating thyroid hormone
→ tachycardia, atrial fibrillation, tremors, muscle weakness
- in humans: hyperthermia, cardiovascular, GIT and neuro signs
- 12yo Golden Retriever – hyperthermic, tachycardic with chronic hyperthyroid signs
→ multi-organ dysfunction → euth
Sheppard-Olivares 2020 – toceranib for treatment of canine thyroid carcinoma
- mPFI – treament naive: 206d
– after prior tx: 1015d
- MST – treatment naive: 563d
– after prior tx: 1082d
- 83.3% of dogs experienced clinical benefit
Jegatheeson 2022 – canine thyroid carcinoma response to I131
- overall response rate: 35.3% (4/66 complete, 8/66 partial)
- vs 70-100% for external beam RT; similar to toceranib
- 76.2% improvement in clinical signs
- median time to max tumour reduction 116d (vs 6-22m for external beam RT)
- mPFI 301d, mOST 564d – response to tx not associated with outcome
- cases that had prior therapy → lower risk of progression
Minimally invasive video-assisted parathyroidectomy in dogs: Technique description and feasibility study
Julia P Sumner 2022
- cadaveric feasibility and 5 clinical cases
- 1.5cm midline incision, 1 finger-width caudal to cricoid → 5mm 30° endoscope
- parathyroidectomy with electrocautery and blunt/sharp dissection
- use of blunt suction-dissector facilitated dissection
Perioperative characteristics, histological diagnosis, and outcome in cats undergoing surgical treatment of primary hyperparathyroidism
Ameet Singh 2019
liptak
pre-op iCa median 1.8mmolL – above ref range in all cats; not correlated to post-op iCa
- pathology: 20/32 (62.5%) parathyroid adenoma, 7/32 (21.9%) PT carcinoma
- post-op complications: 2/32 laryngeal paralysis
- post-op hypercalcemia 6/32 (18.8%)
- MST overall 1109 d
- not associated with pre-op iCa, hypo/hypercalcemia at discharge, carcinoma dx
Incidence, survival time, and surgical treatment of parathyroid carcinomas in dogs: 100 cases (2010-2019)
Erickson 2021
96/100 clinical/incidental hypercalcemia
- clinical signs: pu/pd (44%), hindlimb paresis (22%), lethargy (21%), hyporexia (20%)
- cervical ultrasound: 91/91 detected, 64/91 (70.3%) single, 23/91 (25.3%) 2 nodules
4/91 (4%) ≥3 nodules
- hypercalcemia resolution: 89/96 within 7 days
- hypocalcemia: 34/100 (34%) within 7 days → 3 euthanasia due to refractory hypoCa
- incidence and severity not different to other causes of primary hyperparathyroidism
- 1 metastasis to prescap LN
- survival: MST 735d; estimated 1y 84%, 2y 65%, 3y 51%
- PFS: median 718d; 1y 81%, 2y 63%, 3y 39%
